Skip to main content
Top
Published in: European Journal of Medical Research 1/2024

Open Access 01-12-2024 | Parkinson's Disease | Review

Role of GABA pathway in motor and non-motor symptoms in Parkinson's disease: a bidirectional circuit

Authors: Bandar Alharbi, Hayder M. Al-kuraishy, Ali I. Al-Gareeb, Engy Elekhnawy, Hind Alharbi, Athanasios Alexiou, Marios Papadakis, Gaber El-Saber Batiha

Published in: European Journal of Medical Research | Issue 1/2024

Login to get access

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disease as a result of the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc). The fundamental features of PD are motor and non-motor symptoms. PD symptoms develop due to the disruption of dopaminergic neurotransmitters and other neurotransmitters such as γ-aminobutyric acid (GABA). The potential role of GABA in PD neuropathology concerning the motor and non-motor symptoms of PD was not precisely discussed. Therefore, this review intended to illustrate the possible role of GABA in PD neuropathology regarding motor and non-motor symptoms. The GABA pathway is essential in regulating the inhibitory tone to prevent excessive stimulation of the cerebral cortex. Degeneration of dopaminergic neurons in PD is linked with reducing GABAergic neurotransmission. Decreasing GABA activity promotes mitochondrial dysfunction and oxidative stress, which are highly related to PD neuropathology. Hence, restoring GABA activity by GABA agonists may attenuate the progression of PD motor symptoms. Therefore, dysregulation of GABAergic neurons in the SNpc contributes to developing PD motor symptoms. Besides, PD non-motor symptoms are also related to the dysfunction of the GABAergic pathway, and amelioration of this pathway may reduce PD non-motor symptoms. In conclusion, the deregulation of the GABAergic pathway in PD might be intricate in developing motor and non-motor symptoms. Improving this pathway might be a novel, beneficial approach to control PD symptoms.
Literature
1.
go back to reference Marogianni C, Sokratous M, Dardiotis E, Hadjigeorgiou GM, Bogdanos D, Xiromerisiou G. Neurodegeneration and inflammation—an interesting interplay in Parkinson’s disease. Int J Mol Sci. 2020;21(22):8421.PubMedPubMedCentralCrossRef Marogianni C, Sokratous M, Dardiotis E, Hadjigeorgiou GM, Bogdanos D, Xiromerisiou G. Neurodegeneration and inflammation—an interesting interplay in Parkinson’s disease. Int J Mol Sci. 2020;21(22):8421.PubMedPubMedCentralCrossRef
2.
go back to reference Safiri S, Noori M, Nejadghaderi SA, Mousavi SE, Sullman MJ, Araj-Khodaei M, Singh K, Kolahi AA, Gharagozli K. The burden of Parkinson’s disease in the Middle East and North Africa region, 1990–2019: Results from the global burden of disease study 2019. BMC Public Health. 2023;23(1):107.PubMedPubMedCentralCrossRef Safiri S, Noori M, Nejadghaderi SA, Mousavi SE, Sullman MJ, Araj-Khodaei M, Singh K, Kolahi AA, Gharagozli K. The burden of Parkinson’s disease in the Middle East and North Africa region, 1990–2019: Results from the global burden of disease study 2019. BMC Public Health. 2023;23(1):107.PubMedPubMedCentralCrossRef
3.
go back to reference Cherian A, Divya KP, Vijayaraghavan A. Parkinson’s disease–genetic cause. Curr Opin Neurol. 2023;36(4):292–301.PubMedCrossRef Cherian A, Divya KP, Vijayaraghavan A. Parkinson’s disease–genetic cause. Curr Opin Neurol. 2023;36(4):292–301.PubMedCrossRef
4.
go back to reference Funayama M, Nishioka K, Li Y, Hattori N. Molecular genetics of Parkinson’s disease: contributions and global trends. J Hum Genet. 2023;68(3):125–30.PubMedCrossRef Funayama M, Nishioka K, Li Y, Hattori N. Molecular genetics of Parkinson’s disease: contributions and global trends. J Hum Genet. 2023;68(3):125–30.PubMedCrossRef
5.
go back to reference Yi M, Li J, Jian S, Li B, Huang Z, Shu L, Zhang Y. Quantitative and causal analysis for inflammatory genes and the risk of Parkinson’s disease. Front Immunol. 2023;28(14):1119315.CrossRef Yi M, Li J, Jian S, Li B, Huang Z, Shu L, Zhang Y. Quantitative and causal analysis for inflammatory genes and the risk of Parkinson’s disease. Front Immunol. 2023;28(14):1119315.CrossRef
6.
go back to reference Zirra A, Rao SC, Bestwick J, Rajalingam R, Marras C, Blauwendraat C, Mata IF, Noyce AJ. Gender differences in the prevalence of Parkinson’s disease. Move Disorders Clin Pract. 2023;10(1):86–93.CrossRef Zirra A, Rao SC, Bestwick J, Rajalingam R, Marras C, Blauwendraat C, Mata IF, Noyce AJ. Gender differences in the prevalence of Parkinson’s disease. Move Disorders Clin Pract. 2023;10(1):86–93.CrossRef
7.
go back to reference Aamodt WW, Willis AW, Dahodwala N. Racial and ethnic disparities in parkinson disease: a call to action. Neurol Clin Pract. 2023;13(2):e200138.PubMedCrossRef Aamodt WW, Willis AW, Dahodwala N. Racial and ethnic disparities in parkinson disease: a call to action. Neurol Clin Pract. 2023;13(2):e200138.PubMedCrossRef
8.
go back to reference Zhao Y, Ray A, Portengen L, Vermeulen R, Peters S. Metal exposure and risk of Parkinson’s disease: a systematic review and meta-analysis. Am J Epidemiol. 2023;192:1207–23.PubMedPubMedCentralCrossRef Zhao Y, Ray A, Portengen L, Vermeulen R, Peters S. Metal exposure and risk of Parkinson’s disease: a systematic review and meta-analysis. Am J Epidemiol. 2023;192:1207–23.PubMedPubMedCentralCrossRef
9.
10.
go back to reference Alomair BM, Al-Kuraishy HM, Al-Buhadily AK, Al-Gareeb AI, De Waard M, Elekhnawy E, Batiha GE. Is sitagliptin effective for SARS-CoV-2 infection: false or true prophecy? Inflammopharmacology. 2022;30(6):2411–5.PubMedPubMedCentralCrossRef Alomair BM, Al-Kuraishy HM, Al-Buhadily AK, Al-Gareeb AI, De Waard M, Elekhnawy E, Batiha GE. Is sitagliptin effective for SARS-CoV-2 infection: false or true prophecy? Inflammopharmacology. 2022;30(6):2411–5.PubMedPubMedCentralCrossRef
11.
go back to reference Al-Kuraishy HM, Al-Gareeb AI, Albogami SM, Jean-Marc S, Nadwa EH, Hafiz AA, Negm WA, Kamal M, Al-Jouboury M, Elekhnawy E, Batiha GE. Potential therapeutic benefits of metformin alone and in combination with sitagliptin in the management of type 2 diabetes patients with COVID-19. Pharmaceuticals. 2022;15(11):1361.PubMedPubMedCentralCrossRef Al-Kuraishy HM, Al-Gareeb AI, Albogami SM, Jean-Marc S, Nadwa EH, Hafiz AA, Negm WA, Kamal M, Al-Jouboury M, Elekhnawy E, Batiha GE. Potential therapeutic benefits of metformin alone and in combination with sitagliptin in the management of type 2 diabetes patients with COVID-19. Pharmaceuticals. 2022;15(11):1361.PubMedPubMedCentralCrossRef
12.
go back to reference Candelise N, Schmitz M, Thüne K, Cramm M, Rabano A, Zafar S, Stoops E, Vanderstichele H, Villar-Pique A, Llorens F, Zerr I. Effect of the micro-environment on α-synuclein conversion and implication in seeded conversion assays. Transl Neurodegenerat. 2020;9:1–6. Candelise N, Schmitz M, Thüne K, Cramm M, Rabano A, Zafar S, Stoops E, Vanderstichele H, Villar-Pique A, Llorens F, Zerr I. Effect of the micro-environment on α-synuclein conversion and implication in seeded conversion assays. Transl Neurodegenerat. 2020;9:1–6.
13.
go back to reference Nadwa EH, Al-Kuraishy HM, Al-Gareeb AI, Elekhnawy E, Albogami SM, Alorabi M, Batiha GE, De Waard M. Cholinergic dysfunction in COVID-19: frantic search and hoping for the best. Naunyn Schmiedebergs Arch Pharmacol. 2023;396(3):453–68.PubMedCrossRef Nadwa EH, Al-Kuraishy HM, Al-Gareeb AI, Elekhnawy E, Albogami SM, Alorabi M, Batiha GE, De Waard M. Cholinergic dysfunction in COVID-19: frantic search and hoping for the best. Naunyn Schmiedebergs Arch Pharmacol. 2023;396(3):453–68.PubMedCrossRef
14.
go back to reference Al-Kuraishy HM, Al-Gareeb AI, Elewa YH, Zahran MH, Alexiou A, Papadakis M, Batiha GE. Parkinson’s disease risk and hyperhomocysteinemia: the possible link. Cell Mol Neurobiol. 2023;19:1–7. Al-Kuraishy HM, Al-Gareeb AI, Elewa YH, Zahran MH, Alexiou A, Papadakis M, Batiha GE. Parkinson’s disease risk and hyperhomocysteinemia: the possible link. Cell Mol Neurobiol. 2023;19:1–7.
15.
go back to reference Gómez-Benito M, Granado N, García-Sanz P, Michel A, Dumoulin M, Moratalla R. Modeling Parkinson’s disease with the alpha-synuclein protein. Front Pharmacol. 2020;23(11):356.CrossRef Gómez-Benito M, Granado N, García-Sanz P, Michel A, Dumoulin M, Moratalla R. Modeling Parkinson’s disease with the alpha-synuclein protein. Front Pharmacol. 2020;23(11):356.CrossRef
16.
go back to reference Alotaibi B, El-Masry TA, Elekhnawy E, El-Kadem AH, Saleh A, Negm WA, Abdelkader DH. Aqueous core epigallocatechin gallate PLGA nanocapsules: characterization, antibacterial activity against uropathogens, and in vivo reno-protective effect in cisplatin induced nephrotoxicity. Drug Deliv. 2022;29(1):1848–62.PubMedPubMedCentralCrossRef Alotaibi B, El-Masry TA, Elekhnawy E, El-Kadem AH, Saleh A, Negm WA, Abdelkader DH. Aqueous core epigallocatechin gallate PLGA nanocapsules: characterization, antibacterial activity against uropathogens, and in vivo reno-protective effect in cisplatin induced nephrotoxicity. Drug Deliv. 2022;29(1):1848–62.PubMedPubMedCentralCrossRef
17.
go back to reference Al-Kuraishy HM, Al-Gareeb AI, Alkhuriji AF, Al-Megrin WA, Elekhnawy E, Negm WA, De Waard M, Batiha GE. Investigation of the impact of rosuvastatin and telmisartan in doxorubicin-induced acute cardiotoxicity. Biomed Pharmacother. 2022;1(154): 113673.CrossRef Al-Kuraishy HM, Al-Gareeb AI, Alkhuriji AF, Al-Megrin WA, Elekhnawy E, Negm WA, De Waard M, Batiha GE. Investigation of the impact of rosuvastatin and telmisartan in doxorubicin-induced acute cardiotoxicity. Biomed Pharmacother. 2022;1(154): 113673.CrossRef
18.
go back to reference Batiha GE, Al-Kuraishy HM, Al-Gareeb AI, Elekhnawy E. SIRT1 pathway in Parkinson’s disease: a faraway snapshot but so close. Inflammopharmacology. 2023;31(1):37–56.PubMedCrossRef Batiha GE, Al-Kuraishy HM, Al-Gareeb AI, Elekhnawy E. SIRT1 pathway in Parkinson’s disease: a faraway snapshot but so close. Inflammopharmacology. 2023;31(1):37–56.PubMedCrossRef
19.
go back to reference Al-kuraishy HM, Al-Gareeb AI, Kaushik A, Kujawska M, Ahmed EA, Batiha GE. SARS-COV-2 infection and Parkinson’s disease: possible links and perspectives. J Neurosci Res. 2022;101(6):952–75.CrossRef Al-kuraishy HM, Al-Gareeb AI, Kaushik A, Kujawska M, Ahmed EA, Batiha GE. SARS-COV-2 infection and Parkinson’s disease: possible links and perspectives. J Neurosci Res. 2022;101(6):952–75.CrossRef
20.
go back to reference Abdelaziz A, Sonbol F, Elbanna T, El-Ekhnawy E. Exposure to sublethal concentrations of benzalkonium chloride induces antimicrobial resistance and cellular changes in Klebsiella pneumoniae clinical isolates. Microb Drug Resist. 2019;25(5):631–8.PubMedCrossRef Abdelaziz A, Sonbol F, Elbanna T, El-Ekhnawy E. Exposure to sublethal concentrations of benzalkonium chloride induces antimicrobial resistance and cellular changes in Klebsiella pneumoniae clinical isolates. Microb Drug Resist. 2019;25(5):631–8.PubMedCrossRef
21.
go back to reference Al-Kuraishy HM, Hussian NR, Al-Naimi MS, Al-Gareeb AI, Al-Mamorri F, Al-Buhadily AK. The potential role of pancreatic γ-aminobutyric acid (GABA) in diabetes mellitus: a critical reappraisal. Int J Prevent Med. 2021;12:19. Al-Kuraishy HM, Hussian NR, Al-Naimi MS, Al-Gareeb AI, Al-Mamorri F, Al-Buhadily AK. The potential role of pancreatic γ-aminobutyric acid (GABA) in diabetes mellitus: a critical reappraisal. Int J Prevent Med. 2021;12:19.
22.
go back to reference Elekhnawy E, Negm WA. The potential application of probiotics for the prevention and treatment of COVID-19. Egypt J Med Human Genet. 2022;23(1):1–9.CrossRef Elekhnawy E, Negm WA. The potential application of probiotics for the prevention and treatment of COVID-19. Egypt J Med Human Genet. 2022;23(1):1–9.CrossRef
23.
go back to reference Huang YH, Huang CY. The complexed crystal structure of dihydropyrimidinase reveals a potential interactive link with the neurotransmitter γ-aminobutyric acid (GABA). Biochem Biophys Res Commun. 2022;15(692): 149351. Huang YH, Huang CY. The complexed crystal structure of dihydropyrimidinase reveals a potential interactive link with the neurotransmitter γ-aminobutyric acid (GABA). Biochem Biophys Res Commun. 2022;15(692): 149351.
24.
go back to reference Mahul-Mellier AL, Burtscher J, Maharjan N, Weerens L, Croisier M, Kuttler F, Leleu M, Knott GW, Lashuel HA. The process of Lewy body formation, rather than simply α-synuclein fibrillization, is one of the major drivers of neurodegeneration. Proc Natl Acad Sci. 2020;117(9):4971–82.PubMedPubMedCentralCrossRef Mahul-Mellier AL, Burtscher J, Maharjan N, Weerens L, Croisier M, Kuttler F, Leleu M, Knott GW, Lashuel HA. The process of Lewy body formation, rather than simply α-synuclein fibrillization, is one of the major drivers of neurodegeneration. Proc Natl Acad Sci. 2020;117(9):4971–82.PubMedPubMedCentralCrossRef
25.
go back to reference Lee SE, Lee Y, Lee GH. The regulation of glutamic acid decarboxylases in GABA neurotransmission in the brain. Arch Pharmacal Res. 2019;42:1031–9.CrossRef Lee SE, Lee Y, Lee GH. The regulation of glutamic acid decarboxylases in GABA neurotransmission in the brain. Arch Pharmacal Res. 2019;42:1031–9.CrossRef
26.
go back to reference Tudeau L, Acuña MA, Albisetti GW, Neumann E, Ralvenius WT, Scheurer L, Poe M, Cook JM, Johannssen HC, Zeilhofer HU. Mice lacking spinal α2GABAA receptors: altered GABAergic neurotransmission, diminished GABAergic antihyperalgesia, and potential compensatory mechanisms preventing a hyperalgesic phenotype. Brain Res. 2022;15(1741): 146889. Tudeau L, Acuña MA, Albisetti GW, Neumann E, Ralvenius WT, Scheurer L, Poe M, Cook JM, Johannssen HC, Zeilhofer HU. Mice lacking spinal α2GABAA receptors: altered GABAergic neurotransmission, diminished GABAergic antihyperalgesia, and potential compensatory mechanisms preventing a hyperalgesic phenotype. Brain Res. 2022;15(1741): 146889.
27.
go back to reference Peerboom C, Wierenga CJ. The postnatal GABA shift: a developmental perspective. Neurosci Biobehav Rev. 2021;1(124):179–92.CrossRef Peerboom C, Wierenga CJ. The postnatal GABA shift: a developmental perspective. Neurosci Biobehav Rev. 2021;1(124):179–92.CrossRef
28.
go back to reference Li J, Liu H, Guo F, Guo R, Zhang H, He X, Ming X, Ma X, Shang G, Ji P, Song L. Increased GABAergic projections in the paraventricular nucleus regulate colonic hypersensitivity via oxytocin in a rat model of irritable bowel syndrome. NeuroReport. 2023;34(2):108–15.PubMedCrossRef Li J, Liu H, Guo F, Guo R, Zhang H, He X, Ming X, Ma X, Shang G, Ji P, Song L. Increased GABAergic projections in the paraventricular nucleus regulate colonic hypersensitivity via oxytocin in a rat model of irritable bowel syndrome. NeuroReport. 2023;34(2):108–15.PubMedCrossRef
29.
go back to reference Bäckström T, Das R, Bixo M. Positive GABAA receptor modulating steroids and their antagonists: implications for clinical treatments. J Neuroendocrinol. 2022;34(2): e13013.PubMedCrossRef Bäckström T, Das R, Bixo M. Positive GABAA receptor modulating steroids and their antagonists: implications for clinical treatments. J Neuroendocrinol. 2022;34(2): e13013.PubMedCrossRef
30.
go back to reference Adams NE, Hughes LE, Rouse MA, Phillips HN, Shaw AD, Murley AG, Cope TE, Bevan-Jones WR, Passamonti L, Street D, Holland N. GABAergic cortical network physiology in frontotemporal lobar degeneration. Brain. 2021;144(7):2135–45.PubMedPubMedCentralCrossRef Adams NE, Hughes LE, Rouse MA, Phillips HN, Shaw AD, Murley AG, Cope TE, Bevan-Jones WR, Passamonti L, Street D, Holland N. GABAergic cortical network physiology in frontotemporal lobar degeneration. Brain. 2021;144(7):2135–45.PubMedPubMedCentralCrossRef
31.
go back to reference Sanchez-Mejias E, Nuñez-Diaz C, Sanchez-Varo R, Gomez-Arboledas A, Garcia-Leon JA, Fernandez-Valenzuela JJ, Mejias-Ortega M, Trujillo-Estrada L, Baglietto-Vargas D, Moreno-Gonzalez I, Davila JC. Distinct disease-sensitive GABAergic neurons in the perirhinal cortex of Alzheimer’s mice and patients. Brain Pathol. 2020;30(2):345–63.PubMedCrossRef Sanchez-Mejias E, Nuñez-Diaz C, Sanchez-Varo R, Gomez-Arboledas A, Garcia-Leon JA, Fernandez-Valenzuela JJ, Mejias-Ortega M, Trujillo-Estrada L, Baglietto-Vargas D, Moreno-Gonzalez I, Davila JC. Distinct disease-sensitive GABAergic neurons in the perirhinal cortex of Alzheimer’s mice and patients. Brain Pathol. 2020;30(2):345–63.PubMedCrossRef
32.
go back to reference Uemura N, Marotta NP, Ara J, Meymand ES, Zhang B, Kameda H, Koike M, Luk KC, Trojanowski JQ, Lee VM. α-Synuclein aggregates amplified from patient-derived Lewy bodies recapitulate Lewy body diseases in mice. Nat Communicat. 2023;14(1):6892.CrossRef Uemura N, Marotta NP, Ara J, Meymand ES, Zhang B, Kameda H, Koike M, Luk KC, Trojanowski JQ, Lee VM. α-Synuclein aggregates amplified from patient-derived Lewy bodies recapitulate Lewy body diseases in mice. Nat Communicat. 2023;14(1):6892.CrossRef
34.
go back to reference Koh W, Kwak H, Cheong E, Lee CJ. GABA tone regulation and its cognitive functions in the brain. Nat Rev Neurosci. 2023;24(9):523–39.PubMedCrossRef Koh W, Kwak H, Cheong E, Lee CJ. GABA tone regulation and its cognitive functions in the brain. Nat Rev Neurosci. 2023;24(9):523–39.PubMedCrossRef
35.
go back to reference Vöglein J, Ricard I, Noachtar S, Kukull WA, Dieterich M, Levin J, Danek A. Seizures in Alzheimer’s disease are highly recurrent and associated with a poor disease course. J Neurol. 2020;267:2941–8.PubMedPubMedCentralCrossRef Vöglein J, Ricard I, Noachtar S, Kukull WA, Dieterich M, Levin J, Danek A. Seizures in Alzheimer’s disease are highly recurrent and associated with a poor disease course. J Neurol. 2020;267:2941–8.PubMedPubMedCentralCrossRef
36.
go back to reference Hidisoglu E, Chiantia G, Franchino C, Marcantoni A, Carbone E. Early Alterations of Hippocampal GABAergic synaptic properties induced by Abeta42 Oligomers. In2020 Alzheimer's Association International Conference 2020. ALZ. Hidisoglu E, Chiantia G, Franchino C, Marcantoni A, Carbone E. Early Alterations of Hippocampal GABAergic synaptic properties induced by Abeta42 Oligomers. In2020 Alzheimer's Association International Conference 2020. ALZ.
37.
go back to reference Vazin T, Ball KA, Lu H, Park H, Ataeijannati Y, Head-Gordon T, Poo MM, Schaffer DV. Efficient derivation of cortical glutamatergic neurons from human pluripotent stem cells: a model system to study neurotoxicity in Alzheimer’s disease. Neurobiol Dis. 2014;1(62):62–72.CrossRef Vazin T, Ball KA, Lu H, Park H, Ataeijannati Y, Head-Gordon T, Poo MM, Schaffer DV. Efficient derivation of cortical glutamatergic neurons from human pluripotent stem cells: a model system to study neurotoxicity in Alzheimer’s disease. Neurobiol Dis. 2014;1(62):62–72.CrossRef
38.
go back to reference Govindpani K, Turner C, Waldvogel HJ, Faull RL, Kwakowsky A. Impaired expression of GABA signaling components in the Alzheimer’s disease middle temporal gyrus. Int J Mol Sci. 2020;21(22):8704.PubMedPubMedCentralCrossRef Govindpani K, Turner C, Waldvogel HJ, Faull RL, Kwakowsky A. Impaired expression of GABA signaling components in the Alzheimer’s disease middle temporal gyrus. Int J Mol Sci. 2020;21(22):8704.PubMedPubMedCentralCrossRef
39.
go back to reference Sood A, Preeti K, Fernandes V, Khatri DK, Singh SB. Glia: a major player in glutamate–GABA dysregulation-mediated neurodegeneration. J Neurosci Res. 2021;99(12):3148–89.PubMedCrossRef Sood A, Preeti K, Fernandes V, Khatri DK, Singh SB. Glia: a major player in glutamate–GABA dysregulation-mediated neurodegeneration. J Neurosci Res. 2021;99(12):3148–89.PubMedCrossRef
40.
go back to reference Batiha GE, Al-Gareeb AI, Elekhnawy E, Al-Kuraishy HM. Potential role of lipoxin in the management of COVID-19: a narrative review. Inflammopharmacology. 2022;30(6):1993–2001.PubMedPubMedCentralCrossRef Batiha GE, Al-Gareeb AI, Elekhnawy E, Al-Kuraishy HM. Potential role of lipoxin in the management of COVID-19: a narrative review. Inflammopharmacology. 2022;30(6):1993–2001.PubMedPubMedCentralCrossRef
41.
go back to reference Cao G, Edden RA, Gao F, Li H, Gong T, Chen W, Liu X, Wang G, Zhao B. Reduced GABA levels correlate with cognitive impairment in patients with relapsing-remitting multiple sclerosis. Eur Radiol. 2018;28(3):1140–8.PubMedCrossRef Cao G, Edden RA, Gao F, Li H, Gong T, Chen W, Liu X, Wang G, Zhao B. Reduced GABA levels correlate with cognitive impairment in patients with relapsing-remitting multiple sclerosis. Eur Radiol. 2018;28(3):1140–8.PubMedCrossRef
42.
go back to reference Schumacher H, Meyer T, Prüss H. GABAB receptor encephalitis in a patient diagnosed with amyotrophic lateral sclerosis. BMC Neurol. 2019;19(1):1–3.CrossRef Schumacher H, Meyer T, Prüss H. GABAB receptor encephalitis in a patient diagnosed with amyotrophic lateral sclerosis. BMC Neurol. 2019;19(1):1–3.CrossRef
43.
go back to reference Alrouji M, Al-Kuraishy HM, Al-Buhadily AK, Al-Gareeb AI, Elekhnawy E, Batiha GE. DPP-4 inhibitors and type 2 diabetes mellitus in Parkinson’s disease: a mutual relationship. Pharmacol Rep. 2023;3:1–4. Alrouji M, Al-Kuraishy HM, Al-Buhadily AK, Al-Gareeb AI, Elekhnawy E, Batiha GE. DPP-4 inhibitors and type 2 diabetes mellitus in Parkinson’s disease: a mutual relationship. Pharmacol Rep. 2023;3:1–4.
44.
go back to reference Al-kuraishy HM, Al-Gareeb AI, Elekhnawy E, Batiha GE. Dipyridamole and adenosinergic pathway in Covid-19: a juice or holy grail. Egypt J Med Human Genet. 2022;23(1):140.CrossRef Al-kuraishy HM, Al-Gareeb AI, Elekhnawy E, Batiha GE. Dipyridamole and adenosinergic pathway in Covid-19: a juice or holy grail. Egypt J Med Human Genet. 2022;23(1):140.CrossRef
45.
go back to reference Al-Kuraishy HM, Al-Fakhrany OM, Elekhnawy E, Al-Gareeb AI, Alorabi M, De Waard M, Albogami SM, Batiha GE. Traditional herbs against COVID-19: back to old weapons to combat the new pandemic. Eur J Med Res. 2022;27(1):186.PubMedPubMedCentralCrossRef Al-Kuraishy HM, Al-Fakhrany OM, Elekhnawy E, Al-Gareeb AI, Alorabi M, De Waard M, Albogami SM, Batiha GE. Traditional herbs against COVID-19: back to old weapons to combat the new pandemic. Eur J Med Res. 2022;27(1):186.PubMedPubMedCentralCrossRef
46.
go back to reference Blesa J, Foffani G, Dehay B, Bezard E, Obeso JA. Motor and non-motor circuit disturbances in early Parkinson disease: which happens first? Nat Rev Neurosci. 2022;23(2):115–28.PubMedCrossRef Blesa J, Foffani G, Dehay B, Bezard E, Obeso JA. Motor and non-motor circuit disturbances in early Parkinson disease: which happens first? Nat Rev Neurosci. 2022;23(2):115–28.PubMedCrossRef
47.
go back to reference Gerlach M, Gsell W, Kornhuber J, Jellinger K, Krieger V, Pantucek F, Vock R, Riederer P. A post mortem study on neurochemical markers of dopaminergic, GABA-ergic and glutamatergic neurons in basal ganglia-thalamocortical circuits in Parkinson syndrome. Brain Res. 1996;741(1–2):142–52.PubMedCrossRef Gerlach M, Gsell W, Kornhuber J, Jellinger K, Krieger V, Pantucek F, Vock R, Riederer P. A post mortem study on neurochemical markers of dopaminergic, GABA-ergic and glutamatergic neurons in basal ganglia-thalamocortical circuits in Parkinson syndrome. Brain Res. 1996;741(1–2):142–52.PubMedCrossRef
48.
49.
50.
go back to reference Lemos JC, Friend DM, Kaplan AR, Shin JH, Rubinstein M, Kravitz AV, Alvarez VA. Enhanced GABA transmission drives bradykinesia following loss of dopamine D2 receptor signaling. Neuron. 2016;90(4):824–38.PubMedPubMedCentralCrossRef Lemos JC, Friend DM, Kaplan AR, Shin JH, Rubinstein M, Kravitz AV, Alvarez VA. Enhanced GABA transmission drives bradykinesia following loss of dopamine D2 receptor signaling. Neuron. 2016;90(4):824–38.PubMedPubMedCentralCrossRef
51.
go back to reference Błaszczyk JW. Parkinson’s disease and neurodegeneration: GABA-collapse hypothesis. Front Neurosci. 2016;9(10):269. Błaszczyk JW. Parkinson’s disease and neurodegeneration: GABA-collapse hypothesis. Front Neurosci. 2016;9(10):269.
52.
go back to reference Nath S, Goodwin J, Engelborghs Y, Pountney DL. Raised calcium promotes α-synuclein aggregate formation. Mol Cell Neurosci. 2011;46(2):516–26.PubMedCrossRef Nath S, Goodwin J, Engelborghs Y, Pountney DL. Raised calcium promotes α-synuclein aggregate formation. Mol Cell Neurosci. 2011;46(2):516–26.PubMedCrossRef
53.
go back to reference Yarnall A, Rochester L, Burn DJ. The interplay of cholinergic function, attention, and falls in Parkinson’s disease. Mov Disord. 2011;26(14):2496–503.PubMedCrossRef Yarnall A, Rochester L, Burn DJ. The interplay of cholinergic function, attention, and falls in Parkinson’s disease. Mov Disord. 2011;26(14):2496–503.PubMedCrossRef
54.
go back to reference Leandrou E, Emmanouilidou E, Vekrellis K. Voltage-gated calcium channels and α-synuclein: implications in Parkinson’s disease. Front Mol Neurosci. 2019;9(12):237.CrossRef Leandrou E, Emmanouilidou E, Vekrellis K. Voltage-gated calcium channels and α-synuclein: implications in Parkinson’s disease. Front Mol Neurosci. 2019;9(12):237.CrossRef
55.
go back to reference Ali NH, Alhamdan NA, Al-Kuraishy HM, Al-Gareeb AI, Elekhnawy E, Batiha GE. Irisin/PGC-1α/FNDC5 pathway in Parkinson’s disease: truth under the throes. Naunyn Schmiedebergs Arch Pharmacol. 2023;11:1–1. Ali NH, Alhamdan NA, Al-Kuraishy HM, Al-Gareeb AI, Elekhnawy E, Batiha GE. Irisin/PGC-1α/FNDC5 pathway in Parkinson’s disease: truth under the throes. Naunyn Schmiedebergs Arch Pharmacol. 2023;11:1–1.
56.
go back to reference Hajj R, Milet A, Toulorge D, Cholet N, Laffaire J, Foucquier J, Robelet S, Mitry R, Guedj M, Nabirotchkin S, Chumakov I. Combination of acamprosate and baclofen as a promising therapeutic approach for Parkinson’s disease. Sci Rep. 2015;5(1):1–3.CrossRef Hajj R, Milet A, Toulorge D, Cholet N, Laffaire J, Foucquier J, Robelet S, Mitry R, Guedj M, Nabirotchkin S, Chumakov I. Combination of acamprosate and baclofen as a promising therapeutic approach for Parkinson’s disease. Sci Rep. 2015;5(1):1–3.CrossRef
57.
go back to reference Lozovaya N, Eftekhari S, Cloarec R, Gouty-Colomer LA, Dufour A, Riffault B, Billon-Grand M, Pons-Bennaceur A, Oumar N, Burnashev N, Ben-Ari Y. GABAergic inhibition in dual-transmission cholinergic and GABAergic striatal interneurons is abolished in Parkinson disease. Nat Commun. 2018;9(1):1–4.CrossRef Lozovaya N, Eftekhari S, Cloarec R, Gouty-Colomer LA, Dufour A, Riffault B, Billon-Grand M, Pons-Bennaceur A, Oumar N, Burnashev N, Ben-Ari Y. GABAergic inhibition in dual-transmission cholinergic and GABAergic striatal interneurons is abolished in Parkinson disease. Nat Commun. 2018;9(1):1–4.CrossRef
58.
go back to reference Tyagi RK, Bisht R, Pant J, Majeed AB, Prakash A. Possible role of GABA-B receptor modulation in MPTP induced Parkinson’s disease in rats. Exp Toxicol Pathol. 2015;67(2):211–7.PubMedCrossRef Tyagi RK, Bisht R, Pant J, Majeed AB, Prakash A. Possible role of GABA-B receptor modulation in MPTP induced Parkinson’s disease in rats. Exp Toxicol Pathol. 2015;67(2):211–7.PubMedCrossRef
59.
go back to reference Damier P, Hammond C, Ben-Ari Y. Bumetanide to treat Parkinson disease: a report of 4 cases. Clin Neuropharmacol. 2016;39(1):57–9.PubMedCrossRef Damier P, Hammond C, Ben-Ari Y. Bumetanide to treat Parkinson disease: a report of 4 cases. Clin Neuropharmacol. 2016;39(1):57–9.PubMedCrossRef
60.
go back to reference Daniele A, Panza F, Greco A, Logroscino G, Seripa D. Can a positive allosteric modulation of GABAergic receptors improve motor symptoms in patients with Parkinson’s disease? The potential role of zolpidem in the treatment of Parkinson’s disease. Parkinson’s Disease. 2016;1:2016. Daniele A, Panza F, Greco A, Logroscino G, Seripa D. Can a positive allosteric modulation of GABAergic receptors improve motor symptoms in patients with Parkinson’s disease? The potential role of zolpidem in the treatment of Parkinson’s disease. Parkinson’s Disease. 2016;1:2016.
61.
go back to reference Bohnen NI, Barr J, Vangel R, Roytman S, Paalanen R, Frey KA, Scott PJ, Kanel P. GABAA receptor Benzodiazepine binding sites and motor impairments in Parkinson’s disease. Brain Sci. 2023;13(12):1711.PubMedPubMedCentralCrossRef Bohnen NI, Barr J, Vangel R, Roytman S, Paalanen R, Frey KA, Scott PJ, Kanel P. GABAA receptor Benzodiazepine binding sites and motor impairments in Parkinson’s disease. Brain Sci. 2023;13(12):1711.PubMedPubMedCentralCrossRef
62.
go back to reference van Nuland AJ, den Ouden HE, Zach H, Dirkx MF, van Asten JJ, Scheenen TW, Toni I, Cools R, Helmich RC. GABAergic changes in the thalamocortical circuit in Parkinson’s disease. Hum Brain Mapp. 2020;41(4):1017–29.PubMedCrossRef van Nuland AJ, den Ouden HE, Zach H, Dirkx MF, van Asten JJ, Scheenen TW, Toni I, Cools R, Helmich RC. GABAergic changes in the thalamocortical circuit in Parkinson’s disease. Hum Brain Mapp. 2020;41(4):1017–29.PubMedCrossRef
63.
go back to reference Emir UE, Tuite PJ, Öz G. Elevated pontine and putamenal GABA levels in mild-moderate Parkinson disease detected by 7 tesla proton MRS. PLoS ONE. 2012;7(1): e30918.PubMedPubMedCentralCrossRef Emir UE, Tuite PJ, Öz G. Elevated pontine and putamenal GABA levels in mild-moderate Parkinson disease detected by 7 tesla proton MRS. PLoS ONE. 2012;7(1): e30918.PubMedPubMedCentralCrossRef
64.
go back to reference Luchetti S, Huitinga IS, Swaab DF. Neurosteroid and GABA-A receptor alterations in Alzheimer’s disease, Parkinson’s disease and multiple sclerosis. Neuroscience. 2011;15(191):6–21.CrossRef Luchetti S, Huitinga IS, Swaab DF. Neurosteroid and GABA-A receptor alterations in Alzheimer’s disease, Parkinson’s disease and multiple sclerosis. Neuroscience. 2011;15(191):6–21.CrossRef
65.
go back to reference Wang Y, Zhang QJ, Liu J, Ali U, Gui ZH, Hui YP, Chen L, Wang T. Changes in firing rate and pattern of GABAergic neurons in subregions of the substantia nigra pars reticulata in rat models of Parkinson’s disease. Brain Res. 2010;9(1324):54–63.CrossRef Wang Y, Zhang QJ, Liu J, Ali U, Gui ZH, Hui YP, Chen L, Wang T. Changes in firing rate and pattern of GABAergic neurons in subregions of the substantia nigra pars reticulata in rat models of Parkinson’s disease. Brain Res. 2010;9(1324):54–63.CrossRef
66.
go back to reference Giehrl-Schwab J, Giesert F, Rauser B, Lao CL, Hembach S, Lefort S, Ibarra IL, Koupourtidou C, Luecken MD, Truong DJ, Fischer-Sternjak J. Parkinson’s disease motor symptoms rescue by CRISPRa-reprogramming astrocytes into GABAergic neurons. EMBO Mol Med. 2022;14(5): e14797.PubMedPubMedCentralCrossRef Giehrl-Schwab J, Giesert F, Rauser B, Lao CL, Hembach S, Lefort S, Ibarra IL, Koupourtidou C, Luecken MD, Truong DJ, Fischer-Sternjak J. Parkinson’s disease motor symptoms rescue by CRISPRa-reprogramming astrocytes into GABAergic neurons. EMBO Mol Med. 2022;14(5): e14797.PubMedPubMedCentralCrossRef
67.
go back to reference Chu J, Wagle-Shukla A, Gunraj C, Lang AE, Chen R. Impaired presynaptic inhibition in the motor cortex in Parkinson disease. Neurology. 2009;72(9):842–9.PubMedCrossRef Chu J, Wagle-Shukla A, Gunraj C, Lang AE, Chen R. Impaired presynaptic inhibition in the motor cortex in Parkinson disease. Neurology. 2009;72(9):842–9.PubMedCrossRef
68.
go back to reference Song Y, Gong T, Saleh MG, Mikkelsen M, Wang G, Edden RA. Upper brainstem GABA levels in Parkinson’s disease. Magn Reson Mater Phys Biol Med. 2021;34(5):689–96.CrossRef Song Y, Gong T, Saleh MG, Mikkelsen M, Wang G, Edden RA. Upper brainstem GABA levels in Parkinson’s disease. Magn Reson Mater Phys Biol Med. 2021;34(5):689–96.CrossRef
71.
go back to reference Zhang W, Xiong BR, Zhang LQ, Huang X, Yuan X, Tian YK, Tian XB. The role of the GABAergic system in diseases of the central nervous system. Neuroscience. 2021;21(470):88–99.CrossRef Zhang W, Xiong BR, Zhang LQ, Huang X, Yuan X, Tian YK, Tian XB. The role of the GABAergic system in diseases of the central nervous system. Neuroscience. 2021;21(470):88–99.CrossRef
72.
go back to reference Padilla-Godínez FJ, Ramos-Acevedo R, Martínez-Becerril HA, Bernal-Conde LD, Garrido-Figueroa JF, Hiriart M, Hernández-López A, Argüero-Sánchez R, Callea F, Guerra-Crespo M. Protein misfolding and aggregation: the relatedness between Parkinson’s disease and hepatic endoplasmic reticulum storage disorders. Int J Mol Sci. 2021;22(22):12467.PubMedPubMedCentralCrossRef Padilla-Godínez FJ, Ramos-Acevedo R, Martínez-Becerril HA, Bernal-Conde LD, Garrido-Figueroa JF, Hiriart M, Hernández-López A, Argüero-Sánchez R, Callea F, Guerra-Crespo M. Protein misfolding and aggregation: the relatedness between Parkinson’s disease and hepatic endoplasmic reticulum storage disorders. Int J Mol Sci. 2021;22(22):12467.PubMedPubMedCentralCrossRef
73.
go back to reference Jing XZ, Yuan XZ, Luo X, Zhang SY, Wang XP. An Update on Non-dopaminergic treatments for motor and non-motor symptoms of Parkinson’s disease. Curr Neuropharmacol. 2023;21(8):1806.PubMedPubMedCentralCrossRef Jing XZ, Yuan XZ, Luo X, Zhang SY, Wang XP. An Update on Non-dopaminergic treatments for motor and non-motor symptoms of Parkinson’s disease. Curr Neuropharmacol. 2023;21(8):1806.PubMedPubMedCentralCrossRef
74.
go back to reference Murueta-Goyena A, Andikoetxea A, Gómez-Esteban JC, Gabilondo I. Contribution of the GABAergic system to non-motor manifestations in premotor and early stages of Parkinson’s disease. Front Pharmacol. 2019;30(10):1294.CrossRef Murueta-Goyena A, Andikoetxea A, Gómez-Esteban JC, Gabilondo I. Contribution of the GABAergic system to non-motor manifestations in premotor and early stages of Parkinson’s disease. Front Pharmacol. 2019;30(10):1294.CrossRef
75.
go back to reference Firbank MJ, Parikh J, Murphy N, Killen A, Allan CL, Collerton D, Blamire AM, Taylor JP. Reduced occipital GABA in Parkinson disease with visual hallucinations. Neurology. 2018;91(7):e675–85.PubMedPubMedCentralCrossRef Firbank MJ, Parikh J, Murphy N, Killen A, Allan CL, Collerton D, Blamire AM, Taylor JP. Reduced occipital GABA in Parkinson disease with visual hallucinations. Neurology. 2018;91(7):e675–85.PubMedPubMedCentralCrossRef
76.
go back to reference Haghshomar M, Shobeiri P, Seyedi SA, Abbasi-Feijani F, Poopak A, Sotoudeh H, Kamali A. Cerebellar microstructural abnormalities in Parkinson’s disease: a systematic review of diffusion tensor imaging studies. The Cerebellum. 2022;10:1–27. Haghshomar M, Shobeiri P, Seyedi SA, Abbasi-Feijani F, Poopak A, Sotoudeh H, Kamali A. Cerebellar microstructural abnormalities in Parkinson’s disease: a systematic review of diffusion tensor imaging studies. The Cerebellum. 2022;10:1–27.
77.
go back to reference Lee JY, Martin-Bastida A, Murueta-Goyena A, Gabilondo I, Cuenca N, Piccini P, Jeon B. Multimodal brain and retinal imaging of dopaminergic degeneration in Parkinson disease. Nat Rev Neurol. 2022;18(4):203–20.PubMedCrossRef Lee JY, Martin-Bastida A, Murueta-Goyena A, Gabilondo I, Cuenca N, Piccini P, Jeon B. Multimodal brain and retinal imaging of dopaminergic degeneration in Parkinson disease. Nat Rev Neurol. 2022;18(4):203–20.PubMedCrossRef
78.
go back to reference Russo M, Carrarini C, Dono F, Rispoli MG, Di Pietro M, Di Stefano V, Ferri L, Bonanni L, Sensi SL, Onofrj M. The pharmacology of visual hallucinations in synucleinopathies. Front Pharmacol. 2019;9(10):1379.CrossRef Russo M, Carrarini C, Dono F, Rispoli MG, Di Pietro M, Di Stefano V, Ferri L, Bonanni L, Sensi SL, Onofrj M. The pharmacology of visual hallucinations in synucleinopathies. Front Pharmacol. 2019;9(10):1379.CrossRef
79.
go back to reference Song XM, Hu XW, Li Z, Gao Y, Ju X, Liu DY, Wang QN, Xue C, Cai YC, Bai R, Tan ZL. Reduction of higher-order occipital GABA and impaired visual perception in acute major depressive disorder. Mol Psychiatry. 2021;26(11):6747–55.PubMedPubMedCentralCrossRef Song XM, Hu XW, Li Z, Gao Y, Ju X, Liu DY, Wang QN, Xue C, Cai YC, Bai R, Tan ZL. Reduction of higher-order occipital GABA and impaired visual perception in acute major depressive disorder. Mol Psychiatry. 2021;26(11):6747–55.PubMedPubMedCentralCrossRef
80.
go back to reference Veys L, Vandenabeele M, Ortuno-Lizaran I, Baekelandt V, Cuenca N, Moons L, De Groef L. Retinal α-synuclein deposits in Parkinson’s disease patients and animal models. Acta Neuropathol. 2019;137(3):379–95.PubMedCrossRef Veys L, Vandenabeele M, Ortuno-Lizaran I, Baekelandt V, Cuenca N, Moons L, De Groef L. Retinal α-synuclein deposits in Parkinson’s disease patients and animal models. Acta Neuropathol. 2019;137(3):379–95.PubMedCrossRef
81.
go back to reference Tanik N, Serin HI, Celikbilek A, Inan LE, Gundogdu F. Associations of olfactory bulb and depth of olfactory sulcus with basal ganglia and hippocampus in patients with Parkinson’s disease. Neurosci Lett. 2016;4(620):111–4.CrossRef Tanik N, Serin HI, Celikbilek A, Inan LE, Gundogdu F. Associations of olfactory bulb and depth of olfactory sulcus with basal ganglia and hippocampus in patients with Parkinson’s disease. Neurosci Lett. 2016;4(620):111–4.CrossRef
82.
go back to reference Scherfler C, Esterhammer R, Nocker M, Mahlknecht P, Stockner H, Warwitz B, Spielberger S, Pinter B, Donnemiller E, Decristoforo C, Virgolini I. Correlation of dopaminergic terminal dysfunction and microstructural abnormalities of the basal ganglia and the olfactory tract in Parkinson’s disease. Brain. 2013;136(10):3028–37.PubMedCrossRef Scherfler C, Esterhammer R, Nocker M, Mahlknecht P, Stockner H, Warwitz B, Spielberger S, Pinter B, Donnemiller E, Decristoforo C, Virgolini I. Correlation of dopaminergic terminal dysfunction and microstructural abnormalities of the basal ganglia and the olfactory tract in Parkinson’s disease. Brain. 2013;136(10):3028–37.PubMedCrossRef
83.
84.
go back to reference Chen M, Chen Y, Huo Q, Wang L, Tan S, Misrani A, Jiang J, Chen J, Chen S, Zhang J, Tabassum S. Enhancing GABAergic signaling ameliorates aberrant gamma oscillations of olfactory bulb in AD mouse models. Mol Neurodegener. 2021;16(1):1–23.CrossRef Chen M, Chen Y, Huo Q, Wang L, Tan S, Misrani A, Jiang J, Chen J, Chen S, Zhang J, Tabassum S. Enhancing GABAergic signaling ameliorates aberrant gamma oscillations of olfactory bulb in AD mouse models. Mol Neurodegener. 2021;16(1):1–23.CrossRef
85.
go back to reference Hu B, Geng C, Guo F, Liu Y, Zong YC, Hou XY. GABAA receptor agonist muscimol rescues inhibitory microcircuit defects in the olfactory bulb and improves olfactory function in APP/PS1 transgenic mice. Neurobiol Aging. 2021;1(108):47–57.CrossRef Hu B, Geng C, Guo F, Liu Y, Zong YC, Hou XY. GABAA receptor agonist muscimol rescues inhibitory microcircuit defects in the olfactory bulb and improves olfactory function in APP/PS1 transgenic mice. Neurobiol Aging. 2021;1(108):47–57.CrossRef
86.
go back to reference Rodrigues LS, Fagotti J, Targa AD, Noseda AC, Ilkiw JL, Dorieux FW, Lima MM. Olfactory disturbances in Parkinson's disease. InGenetics, Neurology, Behavior, and Diet in Parkinson's Disease 2020 (pp. 539–552). Academic Press. Rodrigues LS, Fagotti J, Targa AD, Noseda AC, Ilkiw JL, Dorieux FW, Lima MM. Olfactory disturbances in Parkinson's disease. InGenetics, Neurology, Behavior, and Diet in Parkinson's Disease 2020 (pp. 539–552). Academic Press.
87.
go back to reference Svenningsson P, Westman E, Ballard C, Aarsland D. Cognitive impairment in patients with Parkinson’s disease: diagnosis, biomarkers, and treatment. Lancet Neurol. 2012;11(8):697–707.PubMedCrossRef Svenningsson P, Westman E, Ballard C, Aarsland D. Cognitive impairment in patients with Parkinson’s disease: diagnosis, biomarkers, and treatment. Lancet Neurol. 2012;11(8):697–707.PubMedCrossRef
88.
go back to reference Park KW, Jo S, Kim MS, Jeon SR, Ryu HS, Kim J, Park YM, Koh SB, Lee JH, Chung SJ. Genomic association study for cognitive impairment in Parkinson’s disease. Front Neurol. 2021;4(11): 579268.CrossRef Park KW, Jo S, Kim MS, Jeon SR, Ryu HS, Kim J, Park YM, Koh SB, Lee JH, Chung SJ. Genomic association study for cognitive impairment in Parkinson’s disease. Front Neurol. 2021;4(11): 579268.CrossRef
89.
go back to reference Wang W, Mei M, Gao Y, Huang B, Qiu Y, Zhang Y, Wang L, Zhao J, Huang Z, Wang L, Nie K. Changes of brain structural network connection in Parkinson’s disease patients with mild cognitive dysfunction: a study based on diffusion tensor imaging. J Neurol. 2020;267:933–43.PubMedCrossRef Wang W, Mei M, Gao Y, Huang B, Qiu Y, Zhang Y, Wang L, Zhao J, Huang Z, Wang L, Nie K. Changes of brain structural network connection in Parkinson’s disease patients with mild cognitive dysfunction: a study based on diffusion tensor imaging. J Neurol. 2020;267:933–43.PubMedCrossRef
90.
go back to reference Verma G, Bhardwaj A, Aledavood T, De Choudhury M, Kumar S. Examining the impact of sharing COVID-19 misinformation online on mental health. Sci Rep. 2022;12(1):8045.PubMedPubMedCentralCrossRef Verma G, Bhardwaj A, Aledavood T, De Choudhury M, Kumar S. Examining the impact of sharing COVID-19 misinformation online on mental health. Sci Rep. 2022;12(1):8045.PubMedPubMedCentralCrossRef
91.
go back to reference Prévot T, Sibille E. Altered GABA-mediated information processing and cognitive dysfunctions in depression and other brain disorders. Mol Psychiatry. 2021;26(1):151–67.PubMedCrossRef Prévot T, Sibille E. Altered GABA-mediated information processing and cognitive dysfunctions in depression and other brain disorders. Mol Psychiatry. 2021;26(1):151–67.PubMedCrossRef
92.
go back to reference Lanoue AC, Dumitriu A, Myers RH, Soghomonian JJ. Decreased glutamic acid decarboxylase mRNA expression in prefrontal cortex in Parkinson’s disease. Exp Neurol. 2010;226(1):207–17.PubMedPubMedCentralCrossRef Lanoue AC, Dumitriu A, Myers RH, Soghomonian JJ. Decreased glutamic acid decarboxylase mRNA expression in prefrontal cortex in Parkinson’s disease. Exp Neurol. 2010;226(1):207–17.PubMedPubMedCentralCrossRef
93.
go back to reference Nutt JG, Curtze C, Hiller A, Anderson S, Larson PS, Van Laar AD, Richardson RM, Thompson ME, Sedkov A, Leinonen M, Ravina B. Aromatic L-amino acid decarboxylase gene therapy enhances levodopa response in Parkinson’s disease. Mov Disord. 2020;35(5):851–8.PubMedPubMedCentralCrossRef Nutt JG, Curtze C, Hiller A, Anderson S, Larson PS, Van Laar AD, Richardson RM, Thompson ME, Sedkov A, Leinonen M, Ravina B. Aromatic L-amino acid decarboxylase gene therapy enhances levodopa response in Parkinson’s disease. Mov Disord. 2020;35(5):851–8.PubMedPubMedCentralCrossRef
94.
go back to reference Lajoie AC, Lafontaine AL, Kaminska M. The spectrum of sleep disorders in parkinson disease: a review. Chest. 2021;159(2):818–27.PubMedCrossRef Lajoie AC, Lafontaine AL, Kaminska M. The spectrum of sleep disorders in parkinson disease: a review. Chest. 2021;159(2):818–27.PubMedCrossRef
95.
go back to reference Maggi G, Trojano L, Barone P, Santangelo G. Sleep disorders and cognitive dysfunctions in Parkinson’s disease: a meta-analytic study. Neuropsychol Rev. 2021;31(4):643–82.PubMedCrossRef Maggi G, Trojano L, Barone P, Santangelo G. Sleep disorders and cognitive dysfunctions in Parkinson’s disease: a meta-analytic study. Neuropsychol Rev. 2021;31(4):643–82.PubMedCrossRef
96.
go back to reference Wang XT, Yu H, Liu FT, Zhang C, Ma YH, Wang J, Dong Q, Tan L, Wang H, Yu JT. Associations of sleep disorders with cerebrospinal fluid α-synuclein in prodromal and early Parkinson’s disease. J Neurol. 2022;269(5):2469–78.PubMedCrossRef Wang XT, Yu H, Liu FT, Zhang C, Ma YH, Wang J, Dong Q, Tan L, Wang H, Yu JT. Associations of sleep disorders with cerebrospinal fluid α-synuclein in prodromal and early Parkinson’s disease. J Neurol. 2022;269(5):2469–78.PubMedCrossRef
97.
go back to reference Radovanovic L, Petrovic J, Saponjic J. Hippocampal and reticulo-thalamic parvalbumin interneurons and synaptic re-organization during sleep disorders in the rat models of Parkinson’s disease neuropathology. Int J Mol Sci. 2021;22(16):8922.PubMedPubMedCentralCrossRef Radovanovic L, Petrovic J, Saponjic J. Hippocampal and reticulo-thalamic parvalbumin interneurons and synaptic re-organization during sleep disorders in the rat models of Parkinson’s disease neuropathology. Int J Mol Sci. 2021;22(16):8922.PubMedPubMedCentralCrossRef
98.
go back to reference Lim MM, Szymusiak R. Neurobiology of arousal and sleep: updates and insights into neurological disorders. Curr Sleep Med Reports. 2015;1(2):91–100.CrossRef Lim MM, Szymusiak R. Neurobiology of arousal and sleep: updates and insights into neurological disorders. Curr Sleep Med Reports. 2015;1(2):91–100.CrossRef
99.
go back to reference Brickley SG, Franks NP, Wisden W. Modulation of GABAA receptor function and sleep. Curr Opin Physio. 2018;1(2):51–7.CrossRef Brickley SG, Franks NP, Wisden W. Modulation of GABAA receptor function and sleep. Curr Opin Physio. 2018;1(2):51–7.CrossRef
100.
go back to reference Ray S, Agarwal P. Depression and anxiety in Parkinson disease. Clin Geriatr Med. 2020;36(1):93–104.PubMedCrossRef Ray S, Agarwal P. Depression and anxiety in Parkinson disease. Clin Geriatr Med. 2020;36(1):93–104.PubMedCrossRef
101.
go back to reference Iwasawa C, Kuzumaki N, Suda Y, Kagawa R, Oka Y, Hattori N, Okano H, Narita M. Reduced expression of somatostatin in GABAergic interneurons derived from induced pluripotent stem cells of patients with parkin mutations. Mol Brain. 2019;12(1):1–8.CrossRef Iwasawa C, Kuzumaki N, Suda Y, Kagawa R, Oka Y, Hattori N, Okano H, Narita M. Reduced expression of somatostatin in GABAergic interneurons derived from induced pluripotent stem cells of patients with parkin mutations. Mol Brain. 2019;12(1):1–8.CrossRef
102.
go back to reference Dupont E, Christensen SE, Hansen AP, de Fine OB, Orskov H. Low cerebrospinal fluid somatostatin in Parkinson disease: an irreversible abnormality. Neurology. 1982;32(3):312–4.PubMedCrossRef Dupont E, Christensen SE, Hansen AP, de Fine OB, Orskov H. Low cerebrospinal fluid somatostatin in Parkinson disease: an irreversible abnormality. Neurology. 1982;32(3):312–4.PubMedCrossRef
103.
go back to reference Strittmatter M, Hamann GF, Strubel D, Cramer H, Schimrigk K. Somatostatin-like immunoreactivity, its molecular forms and monoaminergic metabolites in aged and demented patients with Parkinson’s disease–effect of L-Dopa. J Neural Transm. 1996;103(5):591–602.PubMedCrossRef Strittmatter M, Hamann GF, Strubel D, Cramer H, Schimrigk K. Somatostatin-like immunoreactivity, its molecular forms and monoaminergic metabolites in aged and demented patients with Parkinson’s disease–effect of L-Dopa. J Neural Transm. 1996;103(5):591–602.PubMedCrossRef
104.
go back to reference Carey G, Görmezoğlu M, de Jong JJ, Hofman PA, Backes WH, Dujardin K, Leentjens AF. Neuroimaging of anxiety in Parkinson’s disease: a systematic review. Mov Disord. 2021;36(2):327–39.PubMedCrossRef Carey G, Görmezoğlu M, de Jong JJ, Hofman PA, Backes WH, Dujardin K, Leentjens AF. Neuroimaging of anxiety in Parkinson’s disease: a systematic review. Mov Disord. 2021;36(2):327–39.PubMedCrossRef
105.
go back to reference Cong S, Xiang C, Zhang S, Zhang T, Wang H, Cong S. Prevalence and clinical aspects of depression in Parkinson’s disease: a systematic review and meta-analysis of 129 studies. Neurosci Biobehav Rev. 2022;21: 104749.CrossRef Cong S, Xiang C, Zhang S, Zhang T, Wang H, Cong S. Prevalence and clinical aspects of depression in Parkinson’s disease: a systematic review and meta-analysis of 129 studies. Neurosci Biobehav Rev. 2022;21: 104749.CrossRef
106.
go back to reference Luscher B, Shen Q, Sahir N. The GABAergic deficit hypothesis of major depressive disorder. Mol Psychiatry. 2011;16(4):383–406.PubMedCrossRef Luscher B, Shen Q, Sahir N. The GABAergic deficit hypothesis of major depressive disorder. Mol Psychiatry. 2011;16(4):383–406.PubMedCrossRef
107.
go back to reference Vieira DS, Naffah-Mazacoratti MG, Zukerman E, Soares CS, Alonso EO, Faulhaber MH, Cavalheiro EA, Peres MF. Cerebrospinal fluid GABA levels in chronic migraine with and without depression. Brain Res. 2006;1090(1):197–201.PubMedCrossRef Vieira DS, Naffah-Mazacoratti MG, Zukerman E, Soares CS, Alonso EO, Faulhaber MH, Cavalheiro EA, Peres MF. Cerebrospinal fluid GABA levels in chronic migraine with and without depression. Brain Res. 2006;1090(1):197–201.PubMedCrossRef
109.
go back to reference Auteri M, Zizzo MG, Serio R. GABA and GABA receptors in the gastrointestinal tract: from motility to inflammation. Pharmacol Res. 2015;1(93):11–21.CrossRef Auteri M, Zizzo MG, Serio R. GABA and GABA receptors in the gastrointestinal tract: from motility to inflammation. Pharmacol Res. 2015;1(93):11–21.CrossRef
110.
go back to reference Auteri M, Zizzo MG, Mastropaolo M, Serio R. Opposite role played by GABAA and GABAB receptors in the modulation of peristaltic activity in mouse distal colon. Eur J Pharmacol. 2014;15(731):93–9.CrossRef Auteri M, Zizzo MG, Mastropaolo M, Serio R. Opposite role played by GABAA and GABAB receptors in the modulation of peristaltic activity in mouse distal colon. Eur J Pharmacol. 2014;15(731):93–9.CrossRef
111.
go back to reference Rossi S, Bartalini S, Ulivelli M. Antiparkinsonian drugs and visual hallucinations. The Lancet Neurology. 2006;1(5):18–9.CrossRef Rossi S, Bartalini S, Ulivelli M. Antiparkinsonian drugs and visual hallucinations. The Lancet Neurology. 2006;1(5):18–9.CrossRef
112.
go back to reference Rivera J, Sharma B, Torres MM, Kumar S. Factors affecting the GABAergic synapse function in Alzheimer’s Disease: focus on microRNAs. Ageing Res Rev. 2023;13: 102123.CrossRef Rivera J, Sharma B, Torres MM, Kumar S. Factors affecting the GABAergic synapse function in Alzheimer’s Disease: focus on microRNAs. Ageing Res Rev. 2023;13: 102123.CrossRef
113.
go back to reference Liu XY, Wang K, Deng XH, Wei YH, Guo R, Liu SF, Zhu YF, Zhong JJ, Zheng JY, Wang MD, Ye QH. Amelioration of olfactory dysfunction in a mouse model of Parkinson’s disease via enhancing GABAergic signaling. Cell Biosci. 2023;13(1):1–20.CrossRef Liu XY, Wang K, Deng XH, Wei YH, Guo R, Liu SF, Zhu YF, Zhong JJ, Zheng JY, Wang MD, Ye QH. Amelioration of olfactory dysfunction in a mouse model of Parkinson’s disease via enhancing GABAergic signaling. Cell Biosci. 2023;13(1):1–20.CrossRef
114.
go back to reference Lai MC, Huang CW. The discordance between network excitability and cognitive performance following vigabatrin treatment during epileptogenesis. Life. 2021;11(11):1213.PubMedPubMedCentralCrossRef Lai MC, Huang CW. The discordance between network excitability and cognitive performance following vigabatrin treatment during epileptogenesis. Life. 2021;11(11):1213.PubMedPubMedCentralCrossRef
115.
go back to reference Liu J, Huang D, Xu J, Tong J, Wang Z, Huang L, Yang Y, Bai X, Wang P, Suo H, Ma Y. Tiagabine protects dopaminergic neurons against neurotoxins by inhibiting microglial activation. Sci Rep. 2015;5(1):15720.PubMedPubMedCentralCrossRef Liu J, Huang D, Xu J, Tong J, Wang Z, Huang L, Yang Y, Bai X, Wang P, Suo H, Ma Y. Tiagabine protects dopaminergic neurons against neurotoxins by inhibiting microglial activation. Sci Rep. 2015;5(1):15720.PubMedPubMedCentralCrossRef
116.
go back to reference El Sabaa RM, Hamdi E, Hamdy NA, Sarhan HA. Effects of levetiracetam compared to valproate on cognitive functions of patients with epilepsy. Neuropsychiatr Dis Treat. 2020;11:1945–53.CrossRef El Sabaa RM, Hamdi E, Hamdy NA, Sarhan HA. Effects of levetiracetam compared to valproate on cognitive functions of patients with epilepsy. Neuropsychiatr Dis Treat. 2020;11:1945–53.CrossRef
117.
go back to reference Naseh M, Bayat M, Akbari S, Vatanparast J, Shabani M, Haghighi AB, Haghani M. Neuroprotective effects of sodium valproate on hippocampal cell and volume, and cognitive function in a rat model of focal cerebral ischemia. Physiol Behav. 2022;1(251): 113806.CrossRef Naseh M, Bayat M, Akbari S, Vatanparast J, Shabani M, Haghighi AB, Haghani M. Neuroprotective effects of sodium valproate on hippocampal cell and volume, and cognitive function in a rat model of focal cerebral ischemia. Physiol Behav. 2022;1(251): 113806.CrossRef
118.
go back to reference Monti B, Gatta V, Piretti F, Raffaelli SS, Virgili M, Contestabile A. Valproic acid is neuroprotective in the rotenone rat model of Parkinson’s disease: involvement of α-synuclein. Neurotox Res. 2010;17:130–41.PubMedCrossRef Monti B, Gatta V, Piretti F, Raffaelli SS, Virgili M, Contestabile A. Valproic acid is neuroprotective in the rotenone rat model of Parkinson’s disease: involvement of α-synuclein. Neurotox Res. 2010;17:130–41.PubMedCrossRef
119.
go back to reference Brugger F, Bhatia KP, Besag FM. Valproate-associated parkinsonism: a critical review of the literature. CNS Drugs. 2016;30:527–40.PubMedCrossRef Brugger F, Bhatia KP, Besag FM. Valproate-associated parkinsonism: a critical review of the literature. CNS Drugs. 2016;30:527–40.PubMedCrossRef
120.
go back to reference Belete D, Jacobs BM, Simonet C, Bestwick JP, Waters S, Marshall CR, Dobson R, Noyce AJ. Association between antiepileptic drugs and incident Parkinson disease. JAMA Neurol. 2023;80(2):183–7.PubMedCrossRef Belete D, Jacobs BM, Simonet C, Bestwick JP, Waters S, Marshall CR, Dobson R, Noyce AJ. Association between antiepileptic drugs and incident Parkinson disease. JAMA Neurol. 2023;80(2):183–7.PubMedCrossRef
121.
go back to reference Hadi F, Agah E, Tavanbakhsh S, Mirsepassi Z, Mousavi SV, Talachi N, Tafakhori A, Aghamollaii V. Safety and efficacy of melatonin, clonazepam, and trazodone in patients with Parkinson’s disease and sleep disorders: a randomized, double-blind trial. Neurol Sci. 2022;43(10):6141–8.PubMedCrossRef Hadi F, Agah E, Tavanbakhsh S, Mirsepassi Z, Mousavi SV, Talachi N, Tafakhori A, Aghamollaii V. Safety and efficacy of melatonin, clonazepam, and trazodone in patients with Parkinson’s disease and sleep disorders: a randomized, double-blind trial. Neurol Sci. 2022;43(10):6141–8.PubMedCrossRef
122.
go back to reference de Almeida CM, Pachito DV, Sobreira-Neto MA, Tumas V, Eckeli AL. Pharmacological treatment for REM sleep behavior disorder in Parkinson disease and related conditions: a scoping review. J Neurol Sci. 2018;15(393):63–8.CrossRef de Almeida CM, Pachito DV, Sobreira-Neto MA, Tumas V, Eckeli AL. Pharmacological treatment for REM sleep behavior disorder in Parkinson disease and related conditions: a scoping review. J Neurol Sci. 2018;15(393):63–8.CrossRef
123.
go back to reference Vadukul DM, Papp M, Thrush RJ, Wang J, Jin Y, Arosio P, Aprile FA. α-Synuclein aggregation is triggered by oligomeric amyloid-β 42 via heterogeneous primary nucleation. J Am Chem Soc. 2023;145(33):18276–85.PubMedPubMedCentralCrossRef Vadukul DM, Papp M, Thrush RJ, Wang J, Jin Y, Arosio P, Aprile FA. α-Synuclein aggregation is triggered by oligomeric amyloid-β 42 via heterogeneous primary nucleation. J Am Chem Soc. 2023;145(33):18276–85.PubMedPubMedCentralCrossRef
124.
go back to reference Bomalaski MN, Claflin ES, Townsend W, Peterson MD. Zolpidem for the treatment of neurologic disorders: a systematic review. JAMA Neurol. 2017;74(9):1130–9.PubMedCrossRef Bomalaski MN, Claflin ES, Townsend W, Peterson MD. Zolpidem for the treatment of neurologic disorders: a systematic review. JAMA Neurol. 2017;74(9):1130–9.PubMedCrossRef
126.
go back to reference Mousten IV, Sørensen NV, Christensen RH, Benros ME. Cerebrospinal fluid biomarkers in patients with unipolar depression compared with healthy control individuals: a systematic review and meta-analysis. JAMA Psychiat. 2022;79:571–81.CrossRef Mousten IV, Sørensen NV, Christensen RH, Benros ME. Cerebrospinal fluid biomarkers in patients with unipolar depression compared with healthy control individuals: a systematic review and meta-analysis. JAMA Psychiat. 2022;79:571–81.CrossRef
127.
go back to reference Nasir M, Trujillo D, Levine J, Dwyer JB, Rupp ZW, Bloch MH. Glutamate systems in DSM-5 anxiety disorders: their role and a review of glutamate and GABA psychopharmacology. Front Psychiat. 2020;11:548505.CrossRef Nasir M, Trujillo D, Levine J, Dwyer JB, Rupp ZW, Bloch MH. Glutamate systems in DSM-5 anxiety disorders: their role and a review of glutamate and GABA psychopharmacology. Front Psychiat. 2020;11:548505.CrossRef
129.
go back to reference Dissanayaka N, Pourzinal D, Byrne GJ, Yang J, McMahon KL, Pontone GM, O’Sullivan JD, Adam R, Littleford R, Chatfield M, Lehn A. Levetiracetam for the treatment of mild cognitive impairment in Parkinson’s disease: a double-blind controlled proof-of-concept trial protocol. Pilot Feasibility Stud. 2023;9(1):189.PubMedPubMedCentralCrossRef Dissanayaka N, Pourzinal D, Byrne GJ, Yang J, McMahon KL, Pontone GM, O’Sullivan JD, Adam R, Littleford R, Chatfield M, Lehn A. Levetiracetam for the treatment of mild cognitive impairment in Parkinson’s disease: a double-blind controlled proof-of-concept trial protocol. Pilot Feasibility Stud. 2023;9(1):189.PubMedPubMedCentralCrossRef
130.
go back to reference Dhir A, Akula KK, Kulkarni SK. Tiagabine, a GABA uptake inhibitor, attenuates 3-nitropropionic acid-induced alterations in various behavioral and biochemical parameters in rats. Prog Neuropsychopharm Biol Psychiatry. 2008;32(3):835–43.CrossRef Dhir A, Akula KK, Kulkarni SK. Tiagabine, a GABA uptake inhibitor, attenuates 3-nitropropionic acid-induced alterations in various behavioral and biochemical parameters in rats. Prog Neuropsychopharm Biol Psychiatry. 2008;32(3):835–43.CrossRef
Metadata
Title
Role of GABA pathway in motor and non-motor symptoms in Parkinson's disease: a bidirectional circuit
Authors
Bandar Alharbi
Hayder M. Al-kuraishy
Ali I. Al-Gareeb
Engy Elekhnawy
Hind Alharbi
Athanasios Alexiou
Marios Papadakis
Gaber El-Saber Batiha
Publication date
01-12-2024
Publisher
BioMed Central
Published in
European Journal of Medical Research / Issue 1/2024
Electronic ISSN: 2047-783X
DOI
https://doi.org/10.1186/s40001-024-01779-7

Other articles of this Issue 1/2024

European Journal of Medical Research 1/2024 Go to the issue