Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Inflammopharmacology
Published in: Inflammopharmacology 2/2024

18-03-2024 | Parkinson's Disease | Review

The effects of cholesterol and statins on Parkinson’s neuropathology: a narrative review

Authors: Hayder M. Al-kuraishy, Esraa H. Fahad, Salah Al-Windy, Suzy A. El-Sherbeni, Walaa A. Negm, Gaber El-Saber Batiha

Published in: Inflammopharmacology | Issue 2/2024

Login to get access

Abstract

Parkinson disease (PD) is chronic and progressive neurodegenerative disease of the brain characterized by motor symptoms including tremors, rigidity, postural instability, and bradykinesia. PD neuropathology is due to the progressive degeneration of dopaminergic neurons in the substantia nigra and accumulation of Lewy bodies in the survival neurons. The brain contains a largest amount of cholesterol which is mainly synthesized from astrocytes and glial cells. Cholesterol is intricate in the pathogenesis of PD and may be beneficial or deleterious. Therefore, there are controversial points concerning the role of cholesterol in PD neuropathology. In addition, cholesterol-lowering agents' statins can affect brain cholesterol. Different studies highlighted that statins, via inhibition of brain HMG-CoA, can affect neuronal integrity through suppression of neuronal cholesterol, which regulates synaptic plasticity and neurotransmitter release. Furthermore, statins affect the development and progression of different neurodegenerative diseases in bidirectional ways that could be beneficial or detrimental. Therefore, the objective of the present review was to clarify the double-sward effects of cholesterol and statins on PD neuropathology.
Literature
Airavaara M, Parkkinen I, Konovalova J, Albert K, Chmielarz P, Domanskyi A (2020) Back and to the future: from neurotoxin-induced to human Parkinson’s disease models. Curr Protoc Neurosci 91(1):e88PubMedCrossRef
Al-kuraishy HM, Al-Gareeb AI, Kaushik A, Kujawska M, Ahmed EA, Batiha GES (2023) SARS-CoV-2 infection and Parkinson’s disease: possible links and perspectives. J Neurosci Res 101(6):952–975PubMedCrossRef
Al-Kuraishy HM, Al-Gareeb AI, Negm WA, Alexiou A, Batiha GE (2022) Ursolic acid and SARS-CoV-2 infection: a new horizon and perspective. Inflammopharmacology 30(5):1493–1501PubMedPubMedCentralCrossRef
Al-Kuraishy HM, Al-Gareeb AI, Saad HM, Batiha GE (2023a) Long-term use of metformin and Alzheimer’s disease: beneficial or detrimental effects. Inflammopharmacology 31:1–9PubMed
Al-Kuraishy HM, Al-Gareeb AI, Saad HM, Batiha GE (2023b) The potential therapeutic effect of statins in multiple sclerosis: beneficial or detrimental effects. Inflammopharmacology 31:1–12PubMedCrossRef
Al-Kuraishy HM, Al-Gareeb AI, Selim HM, Alexiou A, Papadakis M, Negm WA and Batiha GE (2023c) Does vitamin D protect or treat Parkinson’s disease? A narrative review. Naunyn-Schmiedeberg's Archives Pharmacol 396:1–8
Alsubaie N, Al-Kuraishy HM, Al-Gareeb AI, Alharbi B, De Waard M, Sabatier J-M, Saad HM, Batiha GE-S (2022a) Statins use in Alzheimer disease: bane or boon from frantic search and narrative review. Brain Sci 12(10):1290PubMedPubMedCentralCrossRef
Alsubaie N, Al-Kuraishy HM, Al-Gareeb AI, Alharbi B, De Waard M, Sabatier JM, Saad JM, Batiha GE (2022b) Statins use in Alzheimer disease: bane or boon from frantic search and narrative review. Brain Sci 12(10):1290PubMedPubMedCentralCrossRef
Bagheri H, Ghasemi F, Barreto GE, Sathyapalan T, Jamialahmadi T, Sahebkar A (2020) The effects of statins on microglial cells to protect against neurodegenerative disorders: a mechanistic review. BioFactors 46(3):309–325PubMedCrossRef
Batiha GE-S, Al-Kuraishy HM, Al-Gareeb AI, Elekhnawy E (2023) SIRT1 pathway in Parkinson’s disease: a faraway snapshot but so close. Inflammopharmacology 31(1):37–56PubMedCrossRef
Beal MF, Oakes D, Shoulson I, Henchcliffe C, Galpern WR, Haas R, Juncos JL, Nutt JG, Voss TS, Ravina B (2014) A randomized clinical trial of high-dosage coenzyme Q10 in early Parkinson disease: no evidence of benefit. JAMA Neurol 71(5):543–552PubMedCrossRef
Björkhem I, Lövgren-Sandblom A, Leoni V, Meaney S, Brodin L, Salveson L, Winge K, Pålhagen S, Svenningsson P (2013) Oxysterols and Parkinson’s disease: evidence that levels of 24S-hydroxycholesterol in cerebrospinal fluid correlates with the duration of the disease. Neurosci Lett 555:102–105PubMedCrossRef
Blauwendraat C, Nalls MA, Singleton AB (2020) The genetic architecture of Parkinson’s disease. The Lancet Neurology 19(2):170–178PubMedCrossRef
Braak H, Del Tredici K (2017) Neuropathological staging of brain pathology in sporadic Parkinson’s disease: separating the wheat from the chaff. J Parkinsons Dis 7(s1):S71–S85PubMedPubMedCentralCrossRef
Butterfield DA, Barone E, Mancuso C (2011) Cholesterol-independent neuroprotective and neurotoxic activities of statins: perspectives for statin use in Alzheimer disease and other age-related neurodegenerative disorders. Pharmacol Res 64(3):180–186PubMedPubMedCentralCrossRef
Bykov K, Yoshida K, Weisskopf MG, Gagne JJ (2017) Confounding of the association between statins and Parkinson disease: systematic review and meta-analysis. Pharmacoepidemiol Drug Saf 26(3):294–300PubMedCrossRef
Chung SJ, Yoo HS, Lee YH, Lee PH, Sohn YH (2019) Heterogeneous patterns of striatal dopamine loss in patients with young-versus old-onset Parkinson’s disease: impact on clinical features. J Mov Disord 12(2):113PubMedPubMedCentralCrossRef
Clementino AR, Marchi C, Pozzoli M, Bernini F, Zimetti F, Sonvico F (2021) Anti-inflammatory properties of statin-loaded biodegradable lecithin/chitosan nanoparticles: a step toward nose-to-brain treatment of neurodegenerative diseases. Front Pharmacol 12:716380PubMedPubMedCentralCrossRef
Consonni A, Miglietti M, De Luca CMG, Cazzaniga FA, Ciullini A, Dellarole IL, Bufano G, Di Fonzo A, Giaccone G, Baggi F (2022) Approaching the gut and nasal microbiota in Parkinson’s disease in the era of the seed amplification assays. Brain Sci 12(11):1579PubMedPubMedCentralCrossRef
Dickson DW (2018) Neuropathology of Parkinson disease. Parkinsonism Relat Disord 46:30–33CrossRef
Eriksson I, Nath S, Bornefall P, Giraldo AMV, Öllinger K (2017) Impact of high cholesterol in a Parkinson’s disease model: Prevention of lysosomal leakage versus stimulation of α-synuclein aggregation. Eur J Cell Biol 96(2):99–109PubMedCrossRef
Fabelo N, Martín V, Santpere G, Marín R, Torrent L, Ferrer I, Díaz M (2011) Severe alterations in lipid composition of frontal cortex lipid rafts from Parkinson’s disease and incidental Parkinson’s disease. Mol Med 17(9):1107–1118PubMedPubMedCentralCrossRef
Fang F, Zhan Y, Hammar N, Shen X, Wirdefeldt K, Walldius G, Mariosa D (2019) Lipids, apolipoproteins, and the risk of Parkinson disease: a prospective cohort study and a mendelian randomization analysis. Circ Res 125(6):643–652PubMedCrossRef
Fortin DL, Troyer MD, Nakamura K, Kubo SI, Anthony MD, Edwards RH (2004) Lipid rafts mediate the synaptic localization of α-synuclein. J Neurosci 24(30):6715–6723PubMedPubMedCentralCrossRef
Heras-Garvin A, Stefanova N (2020) From synaptic protein to prion: the long and controversial journey of α-synuclein. Front in Synaptic Neurosci 12:584536CrossRef
Hu G, Antikainen R, Jousilahti P, Kivipelto M, Tuomilehto J (2008a) Total cholesterol and the risk of Parkinson disease. Neurology 70(21):1972–1979PubMedCrossRef
Hu G, Antikainen R, Jousilahti P, Kivipelto M, Tuomilehto J (2008b) Total cholesterol and the risk of Parkinson disease. Neurology 70(21):1972–1979PubMedCrossRef
Huang X, Chen H, Miller WC, Mailman RB, Woodard JL, Chen PC, Xiang D, Murrow RW, Wang YZ, Poole C (2007) Lower low-density lipoprotein cholesterol levels are associated with Parkinson’s disease. Movem Disord 22(3):377–381CrossRef
Huang X, Sterling NW, Du G, Sun D, Stetter C, Kong L, Zhu Y, Neighbors J, Lewis MM, Chen H, Hohl RJ (2019) Brain cholesterol metabolism and Parkinson’s disease. Mov Disord 34(3):386–395PubMedPubMedCentralCrossRef
Hussien NR, Al-Niemi MS, Al-Kuraishy HM, Al-Gareeb AI (2021) Statins and covid-19: The neglected front of bidirectional effects. J Pak Med Assoc 71(8):133
Javed H, Meeran MN, Azimullah S, Bader Eddin L, Dwivedi VD, Jha NK, Ojha S (2020) α-Bisabolol, a dietary bioactive phytochemical attenuates dopaminergic neurodegeneration through modulation of oxidative stress, neuroinflammation and apoptosis in rotenone-induced rat model of Parkinson’s disease. Biomolecules 10(10):1421PubMedPubMedCentralCrossRef
Jeong SH, Lee HS, Chung SJ, Yoo HS, Jung JH, Baik K, Lee YH, Sohn YH, Lee PH (2021) Effects of statins on dopamine loss and prognosis in Parkinson’s disease. Brain 144(10):3191–3200PubMedCrossRef
Jeong SM, Jang W, Shin DW (2019) Association of statin use with Parkinson’s disease: dose–response relationship Mov. Disorders 34(7):1014–1021CrossRef
Jiang H, Bai X (2022) Apolipoprotein AI mimetic peptides (ApoAI MP) improve oxidative stress and inflammatory responses in Parkinson’s disease mice. Front Pharmacol 13:966232PubMedPubMedCentralCrossRef
Johnson ME, Stecher B, Labrie V, Brundin L, Brundin P (2019) Triggers, facilitators, and aggravators: redefining Parkinson’s disease pathogenesis. Trends Neurosci 42(1):4–13PubMedCrossRef
Kim JH, Chang IB, Kim YH, Kwon MJ, Kim J-H, Choi HG (2022) Association between statin use and Parkinson’s disease in Korean patients with hyperlipidemia. Parkinsonism Relat Disord 97:15–24PubMedCrossRef
Klemann CJ, Martens GJ, Sharma M, Martens MB, Isacson O, Gasser T, Visser JE, Poelmans G (2017) Integrated molecular landscape of Parkinson’s disease. Npj Parkinson’s Dis. 3(1):14CrossRef
Koob AO, Ubhi K, Paulsson JF, Kelly J, Rockenstein E, Mante M, Adame A, Masliah EJEN (2010) Lovastatin ameliorates α-synuclein accumulation and oxidation in transgenic mouse models of α-synucleinopathies. Exp Neurol 221(2):267–274PubMedCrossRef
Kostis JB, Dobrzynski JM (2019) Statins and erectile dysfunction. World J Men’s Health 37(1):1–3CrossRef
Koutsodendris N, Nelson MR, Rao A, Huang Y (2022) Apolipoprotein E and Alzheimer’s disease: findings, hypotheses, and potential mechanisms. Annu Rev Pathol Mech Dis 17:73–99CrossRef
Kreisler A, Gelé P, Wiart J-F, Lhermitte M, Destée A, Bordet R (2007) Lipid-lowering drugs in the MPTP mouse model of Parkinson’s disease: fenofibrate has a neuroprotective effect, whereas bezafibrate and HMG-CoA reductase inhibitors do not. Brain Res 1135:77–84PubMedCrossRef
Kung H-C, Lin K-J, Kung C-T, Lin T-K (2021) Oxidative stress, mitochondrial dysfunction, and neuroprotection of polyphenols with respect to resveratrol in Parkinson’s disease. Biomedicines 9(8):918PubMedPubMedCentralCrossRef
Lee Y-C, Lin C-H, Wu R-M, Lin M-S, Lin J-W, Chang C-H, Lai M-S (2013) Discontinuation of statin therapy associates with Parkinson disease: a population-based study. Neurology 81(5):410–416PubMedCrossRef
Lewis MM, Albertson RM, Du G, Kong L, Foy A, Huang X (2022) Parkinson’s disease progression and statins: hydrophobicity matters. J Parkinsons Dis 12(3):821–830PubMedPubMedCentralCrossRef
Lin KD, Yang CY, Lee MY, Ho SC, Liu CK, Shin SJ (2016) Statin therapy prevents the onset of Parkinson disease in patients with diabetes. Ann Neurol 80(4):532–540PubMedCrossRef
Liu G, Sterling NW, Kong L, Lewis MM, Mailman RB, Chen H, Leslie D, Huang X (2017) Statins may facilitate Parkinson’s disease: Insight gained from a large, national claims database. Mov Disord 32(6):913–917PubMedPubMedCentralCrossRef
Liu Z, Shen C, Li H, Tong J, Wu Y, Ma Y, Wang J, Wang Z, Li Q, Zhang X (2023) NOD-like receptor NLRC5 promotes neuroinflammation and inhibits neuronal survival in Parkinson’s disease models. J Neuroinflammation 20(1):1–21CrossRef
Lu D, Shen L, Mai H, Zang J, Liu Y, Tsang CK, Li K, Xu A (2019) HMG-CoA reductase inhibitors attenuate neuronal damage by suppressing oxygen glucose deprivation-induced activated microglial cells. Neural Plast 2019:1–15
Miyake Y, Tanaka K, Fukushima W, Sasaki S, Kiyohara C, Tsuboi Y, Yamada T, Oeda T, Miki T, Kawamura N, Sakea N (2011) Dietary intake of metals and risk of Parkinson’s disease: a case-control study in Japan. J Neural Sci 306(1–2):98–102CrossRef
Nakamura K, Mori F, Tanji K, Miki Y, Yamada M, Kakita A, Takahashi H, Utsumi J, Sasaki H, Wakabayashi K (2015) Isopentenyl diphosphate isomerase, a cholesterol synthesizing enzyme, is localized in Lewy bodies. Neuropathology 35(5):432–440PubMedCrossRef
Negida A, Menshawy A, El Ashal G, Elfouly Y, Hani Y, Hegazy Y, Fouda S, Rashad YJC, Targets ND-D (2016) Coenzyme Q10 for patients with Parkinson’s disease: a systematic review and meta-analysis. CNS Neurol Disord-Drug Targets 15(1):45–53PubMedCrossRef
Nguyen TTH, Fournier A, Courtois É, Artaud F, Escolano S, Tubert‐Bitter P, Boutron‐Ruault MC, Degaey I, Roze E, Canonico MJMD (2023) Statin use and incidence of Parkinson's disease in women from the French E3N cohort Study. 38
Olmastroni E, Molari G, De Beni N, Colpani O, Galimberti F, Gazzotti M, Zambon A, Catapano AL, Casula M (2022) Statin use and risk of dementia or Alzheimer’s disease: a systematic review and meta-analysis of observational studies. Eur J Prev Cardiol 29(5):804–814PubMedCrossRef
Ou Z, Pan J, Tang S, Duan D, Yu D, Nong H, Wang Z (2021) Global trends in the incidence, prevalence, and years lived with disability of Parkinson’s disease in 204 countries/territories from 1990 to 2019. Front Public Health 9:776847PubMedPubMedCentralCrossRef
Palermo G, Giannoni S, Giuntini M, Belli E, Frosini D, Siciliano G, Ceravolo R (2021) Statins in Parkinson’s disease: influence on motor progression. J Parkinsons Dis 11(4):1651–1662PubMedCrossRef
Pierzchlińska A, Droździk M, Białecka M (2021) "A possible role for HMG-CoA reductase inhibitors and its association with HMGCR genetic variation in Parkinson’s disease. Int J Mol Sci 22(22):12198PubMedPubMedCentralCrossRef
Poewe W, Seppi K, Tanner CM, Halliday GM, Brundin P, Volkmann J, Schrag A-E, Lang AE (2017) Parkinson disease. Nat Rev Dis Primers 3(1):1–21CrossRef
Rozani V, Gurevich T, Giladi N, El-Ad B, Tsamir J, Hemo B, Peretz C (2018) Higher serum cholesterol and decreased Parkinson’s disease risk: a statin-free cohort study. Mov Disord 33(8):1298–1305PubMedCrossRef
Rueter J, Rimbach G, Huebbe P (2022) Functional diversity of apolipoprotein E: from subcellular localization to mitochondrial function. Cell Mol Life Sci 79(9):499PubMedPubMedCentralCrossRef
Saeedi Saravi SS, Saeedi Saravi SS, Arefidoust A, Dehpour AR (2017) The beneficial effects of HMG-CoA reductase inhibitors in the processes of neurodegeneration. Metab Brain Dis 32:949–965PubMedCrossRef
Schelz Z, Muddather HF, Zupkó I (2023) Repositioning of HMG-CoA reductase inhibitors as adjuvants in the modulation of efflux pump-mediated bacterial and tumor resistance. Antibiotics 12(9):1468PubMedPubMedCentralCrossRef
Schmitt M, Dehay B, Bezard E, Garcia-Ladona FJ (2016) Harnessing the trophic and modulatory potential of statins in a dopaminergic cell line. Synapse 70(3):71–86PubMedCrossRef
Schonhoff AM, Williams GP, Wallen ZD, Standaert DG, Harms AS (2020) Innate and adaptive immune responses in Parkinson’s disease. Prog Brain Res 252:169–216PubMedCrossRef
Stevens KN, Creanor S, Jeffery A, Whone A, Zajicek J, Foggo A, Jones B, Chapman R, Cocking L, Wilks J (2022) Evaluation of simvastatin as a disease-modifying treatment for patients with Parkinson disease: a randomized clinical trial. JAMA Neurol 79(12):1232–1241PubMedPubMedCentralCrossRef
Tan LC, Methawasin K, Tan E-K, Tan JH, Au W-L, Yuan J-M, Koh W-P (2016a) Dietary cholesterol, fats and risk of Parkinson’s disease in the Singapore Chinese health study. J Neurol Neurosurg Psychiatry 87(1):86–92PubMed
Tan W, Xue-bin C, Tian Z, Xiao-wu C, Pei-pei H, Zhi-bin C, Bei-sha T (2016b) Effects of simvastatin on the expression of inducible nitric oxide synthase and brain-derived neurotrophic factor in a lipopolysaccharide-induced rat model of Parkinson disease. Int J Neurosci 126(3):278–286PubMedCrossRef
Varalta V, Picelli A, Fonte C, Amato S, Melotti C, Zatezalo V, Saltuari L, Smania N (2015) Relationship between cognitive performance and motor dysfunction in patients with Parkinson’s disease: a pilot cross-sectional study. Biomed Res Int 2015:1–6CrossRef
Wolozin B, Wang SW, Li N-C, Lee A, Lee TA, Kazis LE (2007) Simvastatin is associated with a reduced incidence of dementia and Parkinson’s disease. BMC Med 5(1):1–11CrossRef
Xiao-dan W, Yong J (2017) A 200-year history of Parkinson’s disease. Chin J Contemp Neurol Neurosurg 17(1):5
Xu B, Fan F, Liu Y, Liu Y, Zhou L, Yu H (2023) Distinct effects of familial Parkinson’s disease-associated mutations on α-synuclein phase separation and amyloid aggregation. Biomolecules 13(5):726PubMedPubMedCentralCrossRef
Zarneshan SN, Fakhri S, Khan H (2022) Targeting Akt/CREB/BDNF signaling pathway by ginsenosides in neurodegenerative diseases: a mechanistic approach. Pharmacol Res 177:106099PubMedCrossRef
Metadata
Title
The effects of cholesterol and statins on Parkinson’s neuropathology: a narrative review
Authors
Hayder M. Al-kuraishy
Esraa H. Fahad
Salah Al-Windy
Suzy A. El-Sherbeni
Walaa A. Negm
Gaber El-Saber Batiha
Publication date
18-03-2024
Publisher
Springer International Publishing
Published in
Inflammopharmacology / Issue 2/2024
Print ISSN: 0925-4692
Electronic ISSN: 1568-5608
DOI
https://doi.org/10.1007/s10787-023-01400-z

Other articles of this Issue 2/2024

Inflammopharmacology 2/2024 Go to the issue

Original Article

Synthesis of novel nonsteroidal anti-inflammatory galloyl β-sitosterol-loaded lignin-capped Ag-based drug

Original Article

D-limonene inhibits peritoneal adhesion formation in rats via anti-inflammatory, anti-angiogenic, and antioxidative effects

Original Article

Neuroprotective mechanism of trans,trans-Farnesol in an ICV-STZ-induced rat model of Alzheimer’s pathology

Original Article

Sulfasalazine promotes ferroptosis through AKT-ERK1/2 and P53-SLC7A11 in rheumatoid arthritis

Original Article

Leaf extracts of eight selected southern African medicinal plants modulate pro-inflammatory cytokine secretion in LPS-stimulated RAW 264.7 macrophages

Original Article

Glabridin reduces neuroinflammation by modulating inflammatory signals in LPS-induced in vitro and in vivo models