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Malaria Journal
Published in: Malaria Journal 1/2021

01-12-2021 | Falciparum Malaria | Research

Transcriptome-based analysis of blood samples reveals elevation of DNA damage response, neutrophil degranulation, cancer and neurodegenerative pathways in Plasmodium falciparum patients

Authors: Akua A. Karikari, Wasco Wruck, James Adjaye

Published in: Malaria Journal | Issue 1/2021

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Abstract

Background

Malaria caused by Plasmodium falciparum results in severe complications including cerebral malaria (CM) especially in children. While the majority of falciparum malaria survivors make a full recovery, there are reports of some patients ending up with neurological sequelae or cognitive deficit.

Methods

An analysis of pooled transcriptome data of whole blood samples derived from two studies involving various P. falciparum infections, comprising mild malaria (MM), non-cerebral severe malaria (NCM) and CM was performed. Pathways and gene ontologies (GOs) elevated in the distinct P. falciparum infections were determined.

Results

In all, 2876 genes were expressed in common between the 3 forms of falciparum malaria, with CM having the least number of expressed genes. In contrast to other research findings, the analysis from this study showed MM share similar biological processes with cancer and neurodegenerative diseases, NCM is associated with drug resistance and glutathione metabolism and CM is correlated with endocannabinoid signalling and non-alcoholic fatty liver disease (NAFLD). GO revealed the terms biogenesis, DNA damage response and IL-10 production in MM, down-regulation of cytoskeletal organization and amyloid-beta clearance in NCM and aberrant signalling, neutrophil degranulation and gene repression in CM. Differential gene expression analysis between CM and NCM showed the up-regulation of neutrophil activation and response to herbicides, while regulation of axon diameter was down-regulated in CM.

Conclusions

Results from this study reveal that P. falciparum-mediated inflammatory and cellular stress mechanisms may impair brain function in MM, NCM and CM. However, the neurological deficits predominantly reported in CM cases could be attributed to the down-regulation of various genes involved in cellular function through transcriptional repression, axonal dysfunction, dysregulation of signalling pathways and neurodegeneration. It is anticipated that the data from this study, might form the basis for future hypothesis-driven malaria research.
Appendix
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Literature
1.
2.
Mukhtar MM, Eisawi OA, Amanfo SA, Elamin EM, Imam ZS, Osman FM, et al. Plasmodium vivax cerebral malaria in an adult patient in Sudan. Malar J. 2019;18:316.PubMedPubMedCentralCrossRef
3.
Eugenin EA, Martiney JA, Berman JW. The malaria toxin hemozoin induces apoptosis in human neurons and astrocytes: potential role in the pathogenesis of cerebral malaria. Brain Res. 2019;1720:146317.
4.
Imai T, Iwawaki T, Akai R, Suzue K, Hirai M, Taniguchi T, et al. Evaluating experimental cerebral malaria using oxidative stress indicator OKD48 mice. Int J Parasitol. 2014;44:681–5.PubMedCrossRef
5.
Kavishe RA, Koenderink JB, Alifrangis M. Oxidative stress in malaria and artemisinin combination therapy: pros and cons. FEBS J. 2017;284:2579–91.PubMedCrossRef
6.
Simão-Gurge RM, Wunderlich G, Cricco JA, Cubillos EFG, Doménech-Carbó A, Cebrián-Torrejón G, et al. Biosynthesis of heme O in intraerythrocytic stages of Plasmodium falciparum and potential inhibitors of this pathway. Sci Rep. 2019;9:19261.PubMedPubMedCentralCrossRef
7.
Nagaraj VA, Sundaram B, Varadarajan NM, Subramani PA, Kalappa DM, Ghosh SK, et al. Malaria parasite-synthesized heme is essential in the mosquito and liver stages and complements host heme in the blood stages of infection. PLoS Pathog. 2013;9:e1003522.
8.
9.
Pishchany G, Skaar EP. Taste for blood: hemoglobin as a nutrient source for pathogens. PLoS Pathog. 2012;8:e1002535.
10.
Slater AF, Cerami A. Inhibition by chloroquine of a novel haem polymerase enzyme activity in malaria trophozoites. Nature. 1992;355:167–9.PubMedCrossRef
11.
Grau GE, Mackenzie CD, Carr RA, Redard M, Pizzolato G, Allasia C, et al. Platelet accumulation in brain microvessels in fatal pediatric cerebral malaria. J Infect Dis. 2003;187:461–6.PubMedCrossRef
12.
Sullivan AD, Ittarat I, Meshnick SR. Patterns of haemozoin accumulation in tissue. Parasitology. 1996;112:285–94.PubMedCrossRef
13.
Kwiatkowski D, Bate CA, Scragg IG, Beattie P, Udalova I, Knight JC. The malarial fever response - pathogenesis, polymorphism and prospects for intervention. Ann Trop Med Parasitol. 1997;91:533–42.PubMedCrossRef
14.
Sherry BA, Alava G, Tracey KJ, Martiney J, Cerami A, Slater AF. Malaria-specific metabolite hemozoin mediates the release of several potent endogenous pyrogens (TNF, MIP-1 alpha, and MIP-1 beta) in vitro, and altered thermoregulation in vivo. J Inflamm. 1995;45:85–96.PubMed
15.
Ihekwereme CP, Esimone CO, Nwanegbo EC. Hemozoin inhibition and control of clinical malaria. Adv Pharmacol Sci. 2014;984150.
16.
Polimeni M, Prato M. Host matrix metalloproteinases in cerebral malaria: new kids on the block against blood-brain barrier integrity? Fluids Barriers CNS. 2014;11:1.PubMedPubMedCentralCrossRef
17.
18.
Bhandary B, Marahatta A, Kim H-R, Chae H-J. An Involvement of oxidative stress in endoplasmic reticulum stress and its associated diseases. Int J Mol Sci. 2012;14:434–56.PubMedPubMedCentralCrossRef
19.
Hussain T, Tan B, Yin Y, Blachier F, Tossou MCB, Rahu N. Oxidative stress and inflammation: what polyphenols can do for us? Oxid Med Cell Longev. 2016;2016:7432797.PubMedPubMedCentralCrossRef
20.
Muthuswamy AD, Vedagiri K, Ganesan M, Chinnakannu P. Oxidative stress-mediated macromolecular damage and dwindle in antioxidant status in aged rat brain regions: role of L-carnitine and DL-alpha-lipoic acid. Clin Chim Acta. 2006;368:84–92.PubMedCrossRef
21.
22.
Redza-Dutordoir M, Averill-Bates DA. Activation of apoptosis signalling pathways by reactive oxygen species. Biochim Biophys Acta. 2016;1863:2977–92.PubMedCrossRef
23.
Hegde ML, Hegde PM, Rao KS, Mitra S. Oxidative genome damage and its repair in neurodegenerative diseases: function of transition metals as a double-edged sword. J Alzheimers Dis. 2011;24(Suppl 2):183–98.PubMedPubMedCentralCrossRef
24.
25.
Sertan Copoglu U, Virit O, Hanifi Kokacya M, Orkmez M, Bulbul F, Binnur Erbagci A, et al. Increased oxidative stress and oxidative DNA damage in non-remission schizophrenia patients. Psychiatry Res. 2015;229:200–5.PubMedCrossRef
26.
Singh A, Kukreti R, Saso L, Kukreti S. Oxidative stress: a key modulator in neurodegenerative diseases. Molecules. 2019;24:1583.PubMedCentralCrossRef
27.
Li J, Shang Y, Wang L, Zhao B, Sun C, Li J, et al. Genome integrity and neurogenesis of postnatal hippocampal neural stem/progenitor cells require a unique regulator Filia. Sci Adv. 2020;6:eaba0682.
28.
Thiam A, Sanka M, Ndiaye Diallo R, Torres M, Mbengue B, Nunez NF, et al. Gene expression profiling in blood from cerebral malaria patients and mild malaria patients living in Senegal. BMC Med Genomics. 2019;2:148.CrossRef
29.
Cabantous S, Poudiougou B, Bergon A, Barry A, Oumar AA, Traore AM, et al. Understanding human cerebral malaria through a blood transcriptomic signature: evidences for erythrocyte alteration, immune/inflammatory dysregulation, and brain dysfunction. Mediators Inflamm. 2020;2020:3280689.PubMedPubMedCentralCrossRef
30.
Boldt ABW, van Tong H, Grobusch MP, Kalmbach Y, Dzeing Ella A, Kombila M, et al. The blood transcriptome of childhood malaria. EBioMedicine. 2019;40:614–25.PubMedPubMedCentralCrossRef
31.
Gentleman RC, Carey VJ, Bates DM, Bolstad B, Dettling M, Dudoit S, et al. Bioconductor: open software development for computational biology and bioinformatics. Genome Biol. 2004;5:R80.PubMedPubMedCentralCrossRef
32.
Smyth GK. Linear models and empirical bayes methods for assessing differential expression in microarray experiments. Stat Appl Genet Mol Biol. 2004;3:3.CrossRef
33.
Gautier L, Cope L, Bolstad BM, Irizarry RA. affy–analysis of Affymetrix GeneChip data at the probe level. Bioinformatics. 2004;20:307–15.PubMedCrossRef
34.
Johnson WE, Li C, Rabinovic A. Adjusting batch effects in microarray expression data using empirical Bayes methods. Biostatistics. 2007;8:118–27.PubMedCrossRef
35.
Leek JT, Johnson WE, Parker HS, Jaffe AE, Storey JD. The sva package for removing batch effects and other unwanted variation in high-throughput experiments. Bioinformatics. 2012;28:882–3.PubMedPubMedCentralCrossRef
36.
Storey JD. A direct approach to false discovery rates. J R Stat Soc Series B Stat Methodol. 2002;64:479–98.CrossRef
37.
Warnes GR, Bolker B, Bonebakker L, Gentleman R, Liaw WHA, Lumley T, et al. Gplots: various R programming tools for plotting data. 2016. R package version 2014, 2.
38.
39.
Kanehisa M, Furumichi M, Tanabe M, Sato Y, Morishima K. KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res. 2017;45:D353–61.PubMedCrossRef
40.
Falcon S, Gentleman R. Using GOstats to test gene lists for GO term association. Bioinformatics. 2007;23:257–8.PubMedCrossRef
41.
Wickham H. ggplot2: Elegant Graphics for Data Analysis. Incorporated: Springer Publishing Company; 2009.CrossRef
42.
Zhou Y, Zhou B, Pache L, Chang M, Khodabakhshi AH, Tanaseichuk O, et al. Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat Commun. 2019;10:1523.PubMedPubMedCentralCrossRef
43.
Han H, Cho JW, Lee S, Yun A, Kim H, Bae D, et al. TRRUST v2: an expanded reference database of human and mouse transcriptional regulatory interactions. Nucleic Acids Res. 2018;46:D380–6.PubMedCrossRef
44.
Sampaio NG, Emery SJ, Garnham AL, Tan QY, Sisquella X, Pimentel MA, et al. Extracellular vesicles from early stage Plasmodium falciparum-infected red blood cells contain PfEMP1 and induce transcriptional changes in human monocytes. Cell Microbiol. 2018;20:e12822.
45.
Cavallini A, Brewerton S, Bell A, Sargent S, Glover S, Hardy C, et al. An unbiased approach to identifying tau kinases that phosphorylate tau at sites associated with Alzheimer disease. J Biol Chem. 2013;288:23331–47.PubMedPubMedCentralCrossRef
46.
Morshed N, Lee M, Rodriguez FH, Lauffenburger DA, Mastroeni D, White F. Quantitative phosphoproteomics uncovers dysregulated kinase networks in Alzheimer’s disease. Nat Aging. 2021;1:550–65.CrossRef
47.
Knackstedt SL, Georgiadou A, Apel F, Abu-Abed U, Moxon CA, Cunnington AJ, et al. Neutrophil extracellular traps drive inflammatory pathogenesis in malaria. Sci Immunol. 2019;4:eaaw0336.
48.
49.
Marvin RG, Wolford JL, Kidd MJ, Murphy S, Ward J, Que EL, et al. Fluxes in “free” and total zinc are essential for progression of intraerythrocytic stages of Plasmodium falciparum. Chem Biol. 2012;19:731–41.PubMedPubMedCentralCrossRef
50.
Cai C, Langfelder P, Fuller TF, Oldham MC, Luo R, van den Berg LH, et al. Is human blood a good surrogate for brain tissue in transcriptional studies? BMC Genomics. 2010;11:589.PubMedPubMedCentralCrossRef
51.
Bartoloni A, Zammarchi L. Clinical aspects of uncomplicated and severe malaria. Mediterr J Hematol Infect Dis. 2012;4:e2012026.
52.
53.
Taylor TE, Fu WJ, Carr RA, Whitten RO, Mueller JS, Fosiko NG, et al. Differentiating the pathologies of cerebral malaria by postmortem parasite counts. Nat Med. 2004;10:143–5.PubMedCrossRef
54.
Long CA, Zavala F. Immune responses in malaria. Cold Spring Harb Perspect Med. 2017;7:a025577.
55.
Galluzzi L, Diotallevi A, Magnani M. Endoplasmic reticulum stress and unfolded protein response in infection by intracellular parasites. Future Sci OA. 2017;3:FSO198.
56.
Narsaria N, Mohanty C, Das BK, Mishra SP, Prasad R. Oxidative stress in children with severe malaria. J Trop Pediatr. 2011;58:147–50.PubMedCrossRef
57.
McHugh E, Carmo OMS, Blanch A, Looker O, Liu B, Tiash S, et al. Role of Plasmodium falciparum protein GEXP07 in Maurer's cleft morphology, knob architecture, and P. falciparum EMP1 trafficking. mBio. 2020;11:e03320–19.
58.
Taraschi TF, Trelka D, Martinez S, Schneider T, O’Donnell ME. Vesicle-mediated trafficking of parasite proteins to the host cell cytosol and erythrocyte surface membrane in Plasmodium falciparum infected erythrocytes. Int J Parasitol. 2001;31:1381–91.PubMedCrossRef
59.
Idro R, Kakooza-Mwesige A, Asea B, Ssebyala K, Bangirana P, Opoka RO, et al. Cerebral malaria is associated with long-term mental health disorders: a cross sectional survey of a long-term cohort. Malar J. 2016;15:184.PubMedPubMedCentralCrossRef
60.
Jain K, Sood S, Gowthamarajan K. Modulation of cerebral malaria by curcumin as an adjunctive therapy. Braz J Infect Dis. 2013;7:579–91.CrossRef
61.
62.
Holding PA, Snow RW. Impact of Plasmodium falciparum malaria on performance and learning: review of the evidence. Am J Trop Med Hyg. 2001;64:68–75.PubMedCrossRef
63.
Kihara M, Carter JA, Newton CR. The effect of Plasmodium falciparum on cognition: a systematic review. Trop Med Int Health. 2006;11:386–97.PubMedCrossRef
64.
Hickson MR, Conroy AL, Bangirana P, Opoka RO, Idro R, Ssenkusu JM, et al. Acute kidney injury in Ugandan children with severe malaria is associated with long-term behavioral problems. PLoS One. 2019;14:e0226405.
65.
Guha SK, Tillu R, Sood A, Patgaonkar M, Nanavaty IN, Sengupta A, et al. Single episode of mild murine malaria induces neuroinflammation, alters microglial profile, impairs adult neurogenesis, and causes deficits in social and anxiety-like behavior. Brain Behav Immun. 2014;42:12337.CrossRef
66.
Yusuf FH, Hafiz MY, Shoaib M, Ahmed SA. Cerebral malaria: insight into pathogenesis, complications and molecular biomarkers. Infect Drug Resist. 2017;10:57–9.PubMedPubMedCentralCrossRef
67.
Seydel KB, Kampondeni SD, Valim C, Potchen MJ, Milner DA, Muwalo FW, et al. Brain swelling and death in children with cerebral malaria. N Engl J Med. 2015;372:1126–37.PubMedPubMedCentralCrossRef
68.
Robbiani Davide F, Deroubaix S, Feldhahn N, Oliveira Thiago Y, Callen E, Wang Q, et al. Plasmodium infection promotes genomic instability and AID-dependent B- cell lymphoma. Cell. 2015;162:727–37.PubMedPubMedCentralCrossRef
69.
70.
Keller CC, Kremsner PG, Hittner JB, Misukonis MA, Weinberg JB, Perkins DJ. Elevated nitric oxide production in children with malarial anemia: hemozoin-induced nitric oxide synthase type 2 transcripts and nitric oxide in blood mononuclear cells. Infect Immun. 2004;72:4868–73.PubMedPubMedCentralCrossRef
71.
Sharma V, Collins LB, Chen T-H, Herr N, Takeda S, Sun W, et al. Oxidative stress at low levels can induce clustered DNA lesions leading to NHEJ mediated mutations. Oncotarget. 2016;7:25377–90.PubMedPubMedCentralCrossRef
72.
73.
Huang S-Y, Fang C-Y, Wu C-C, Tsai C-H, Lin S-F, Chen J-Y. Reactive oxygen species mediate epstein-barr virus reactivation by N-Methyl-N’-Nitro-N-Nitrosoguanidine. PLoS One. 2013;8:e84919.
74.
Lassoued S, Ben Ameur R, Ayadi W, Gargouri B, Ben Mansour R, Attia H. Epstein-Barr virus induces an oxidative stress during the early stages of infection in B lymphocytes, epithelial, and lymphoblastoid cell lines. Mol Cell Biochem. 2008;313:179–86.PubMedCrossRef
75.
Bujdoso R, Landgraf M, Jackson WS, Thackray AM. Prion-induced neurotoxicity: possible role for cell cycle activity and DNA damage response. World J Virol. 2015;4:188–97.PubMedPubMedCentralCrossRef
76.
Romphosri S, Changruenngam S, Chookajorn T, Modchang C. Role of a concentration gradient in malaria drug resistance evolution: a combined within- and between-hosts modelling approach. Sci Rep. 2020;10:6219.PubMedPubMedCentralCrossRef
77.
Nies AT. The role of membrane transporters in drug delivery to brain tumors. Cancer Lett. 2007;254:11–29.PubMedCrossRef
78.
Nies AT, Schwab M, Keppler D. Interplay of conjugating enzymes with OATP uptake transporters and ABCC/MRP efflux pumps in the elimination of drugs. Expert Opin Drug Metab Toxicol. 2008;4:545–68.PubMedCrossRef
79.
Kerb R, Fux R, Mörike K, Kremsner PG, Gil JP, Gleiter CH. Pharmacogenetics of antimalarial drugs: effect on metabolism and transport. Lancet Infect Dis. 2009;9:760–74.PubMedCrossRef
80.
Zuluaga L, Pabón A, López C, Ochoa A, Blair S. Amodiaquine failure associated with erythrocytic glutathione in Plasmodium falciparum malaria. Malar J. 2007;6:47.PubMedPubMedCentralCrossRef
81.
Ginsburg H, Golenser J. Glutathione is involved in the antimalarial action of chloroquine and its modulation affects drug sensitivity of human and murine species of Plasmodium. Redox Rep. 2003;8:276–9.PubMedCrossRef
82.
Daoud H, Rouleau GA. A role for ubiquilin 2 mutations in neurodegeneration. Nat Rev Neurol. 2011;7:599–600.PubMedCrossRef
83.
Qi S, Wang C, Li C, Wang P, Liu M. Candidate genes investigation for severe nonalcoholic fatty liver disease based on bioinformatics analysis. Medicine 2017; 96:e7743.
84.
Wu M, Fang K, Wang W, Lin W, Guo L, Wang J. Identification of key genes and pathways for Alzheimer’s disease via combined analysis of genome-wide expression profiling in the hippocampus. Biophys Rep. 2019;5:98–109.CrossRef
85.
Karbalaei R, Allahyari M, Rezaei-Tavirani M, Asadzadeh-Aghdaei H, Zali MR. Protein-protein interaction analysis of Alzheimers disease and NAFLD based on systems biology methods unhide common ancestor pathways. Gastroenterol Hepatol Bed Bench. 2018;11:27.PubMedPubMedCentral
86.
Schwabe RF. Endocannabinoids promote hepatic lipogenesis and steatosis through CB1 receptors. Hepatology. 2005;42:959–61.CrossRef
87.
Jeong WI, Osei-Hyiaman D, Park O, Liu J, Bátkai S, Mukhopadhyay P, et al. Paracrine activation of hepatic CB1 receptors by stellate cell-derived endocannabinoids mediates alcoholic fatty liver. Cell Metab. 2008;7:227–35.PubMedCrossRef
88.
Alferink J, Specht S, Arends H, Schumak B, Schmidt K, Ruland C, et al. Cannabinoid receptor 2 modulates susceptibility to experimental cerebral malaria through a CCL17-dependent mechanism. J Biol Chem. 2016;291:19517–31.PubMedPubMedCentralCrossRef
89.
Cabral GA, Griffin-Thomas L: Emerging role of the cannabinoid receptor CB2 in immune regulation: therapeutic prospects for neuroinflammation. Expert Rev Mol Med. 2009;11:e3.
90.
Centonze D, Rossi S, Finazzi-Agrò A, Bernardi G, Maccarrone M. The (endo)cannabinoid system in multiple sclerosis and amyotrophic lateral sclerosis. Int Rev Neurobiol. 2007;82:171–86.PubMedCrossRef
91.
Rossi S, Bernardi G, Centonze D. The endocannabinoid system in the inflammatory and neurodegenerative processes of multiple sclerosis and of amyotrophic lateral sclerosis. Exp Neurol. 2010;224:92–102.PubMedCrossRef
92.
Fowler CJ, Rojo ML, Rodriguez-Gaztelumendi A. Modulation of the endocannabinoid system: neuroprotection or neurotoxicity? Exp Neurol. 2010;224:37–47.PubMedCrossRef
93.
Surowiec I, Gouveia-Figueira S, Orikiiriza J, Lindquist E, Bonde M, Magambo J, et al. The oxylipin and endocannabidome responses in acute phase Plasmodium falciparum malaria in children. Malar J. 2017;16:358.PubMedPubMedCentralCrossRef
94.
Boeuf PS, Loizon S, Awandare GA, Tetteh JKA, Addae MM, Adjei GO, et al. Insights into deregulated TNF and IL-10 production in malaria: implications for understanding severe malarial anaemia. Malar J. 2012;11:253.PubMedPubMedCentralCrossRef
95.
Son Y, Cheong Y-K, Kim N-H, Chung H-T, Kang DG, Pae H-O. Mitogen-activated protein kinases and reactive oxygen species: How can ros activate MAPK pathways? J Signal Transduct. 2011;2011:792639.
96.
Puig B, Gómez-Isla T, Ribe E, Cuadrado M, Torrejón-Escribano B, Dalfo E. Expression of stress-activated kinases c-Jun N-terminal kinase (SAPK/JNK-P) and p38 kinase (p38-P), and tau hyperphosphorylation in neurites surrounding βA plaques in APP Tg2576 mice. Neuropathol Appl Neurobiol. 2004;30:491–502.PubMedCrossRef
97.
Chiarini A, Pra ID, Marconi M, Chakravarthy B, Whitfield JF, Armato U. Calcium-sensing receptor (CaSR) in human brain’s pathophysiology: roles in late-onset Alzheimer’s disease (LOAD). Curr Pharm Biotechnol. 2009;10:317–26.PubMedCrossRef
98.
Hashimoto Y, Tsuji O, Niikura T, Yamagishi Y, Ishizaka M, Kawasumi M, et al. Involvement of c-Jun N-terminal kinase in amyloid precursor protein-mediated neuronal cell death. J Neurochem. 2003;84:864–77.PubMedCrossRef
99.
Brownlees J, Yates A, Bajaj N, Davis D, Anderton B, Leigh P, et al. Phosphorylation of neurofilament heavy chain side-arms by stress activated protein kinase-1b/Jun N-terminal kinase-3. J Cell Sci. 2000;113:401–7.PubMedCrossRef
100.
Ackerley S, Grierson AJ, Banner S, Perkinton MS, Brownlees J, Byers HL, et al. p38α stress-activated protein kinase phosphorylates neurofilaments and is associated with neurofilament pathology in amyotrophic lateral sclerosis. Mol Cell Neurosci. 2004;26:354–64.PubMedCrossRef
101.
Kim EK, Choi E-J. Pathological roles of MAPK signaling pathways in human diseases. Biochim Biophys Acta. 2010;1802:396–405.PubMedCrossRef
102.
Wang J-Z, Liu F. Microtubule-associated protein tau in development, degeneration and protection of neurons. Prog Neurobiol. 2008;85:148–75.PubMedCrossRef
103.
Pérez M, Morán MA, Ferrer I, Ávila J, Gómez-Ramos P. Phosphorylated tau in neuritic plaques of APP sw/Tau vlw transgenic mice and Alzheimer disease. Acta Neuropathol. 2008;116:409–18.PubMedCrossRef
104.
Eckermann K, Mocanu M-M, Khlistunova I, Biernat J, Nissen A, Hofmann A, et al. The β-propensity of Tau determines aggregation and synaptic loss in inducible mouse models of tauopathy. J Biol Chem. 2007;282:31755–65.PubMedCrossRef
105.
Alonso AD, Cohen LS, Corbo C, Morozova V, ElIdrissi A, Phillips G, et al. Hyperphosphorylation of Tau associates with changes in its function beyond microtubule stability. Front Cell Neurosci. 2018;12:338.PubMedPubMedCentralCrossRef
106.
Dorovini-Zis K, Schmidt K, Huynh H, Fu W, Whitten RO, Milner D, et al. The neuropathology of fatal cerebral malaria in malawian children. Am J Pathol. 2011;178:2146–58.PubMedPubMedCentralCrossRef
107.
Severe malaria. Trop Med Int Health. 2014;19 Suppl 1:7–131.
108.
109.
Maude RJ, Barkhof F, Hassan MU, Ghose A, Hossain A, Abul Faiz M, et al. Magnetic resonance imaging of the brain in adults with severe falciparum malaria. Malar J. 2014;13:177.PubMedPubMedCentralCrossRef
110.
Kumar SP, Babu PP. Aberrant dopamine receptor signaling plays critical role in the impairment of striatal neurons in experimental cerebral malaria. Mol Neurobiol. 2020;57:5069–83.
111.
Aarts E, van Holstein M, Cools R. Striatal dopamine and the interface between motivation and cognition. Front Psychol. 2011;282:248–57.
112.
113.
Manda-Handzlik A, Demkow U. The brain entangled: the contribution of neutrophil extracellular traps to the diseases of the central nervous system. Cells. 2019;8:1477.PubMedCentralCrossRef
114.
Kojima S, Nagamine Y, Hayano M, Looareesuwan S, Nakanishi K. A potential role of interleukin 18 in severe falciparum malaria. Acta Trop. 2004;89:279–84.PubMedCrossRef
115.
Ponts N, Yang J, Chung D-WD, Prudhomme J, Girke T, Horrocks P, et al. Deciphering the ubiquitin-mediated pathway in apicomplexan parasites: a potential strategy to interfere with parasite virulence. PLoS One. 2008;3:e2386.
116.
Zhu X, Cho ES, Sha Q, Peng J, Oksov Y, Kam SY, et al. Giant axon formation in mice lacking Kell, XK, or Kell and XK: animal models of McLeod neuroacanthocytosis syndrome. Am J Pathol. 2014;184:800–7.PubMedPubMedCentralCrossRef
117.
Tanaka K, Suzuki T, Hattori N, Mizuno Y. Ubiquitin, proteasome and parkin. Biochim Biophys Acta. 2004;695:235–47.CrossRef
Metadata
Title
Transcriptome-based analysis of blood samples reveals elevation of DNA damage response, neutrophil degranulation, cancer and neurodegenerative pathways in Plasmodium falciparum patients
Authors
Akua A. Karikari
Wasco Wruck
James Adjaye
Publication date
01-12-2021
Publisher
BioMed Central
Published in
Malaria Journal / Issue 1/2021
Electronic ISSN: 1475-2875
DOI
https://doi.org/10.1186/s12936-021-03918-5

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New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

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