Presumptive Molecular Interconnections Between COVID-19 And Huntington’s Disease

Yıl 2024, Cilt: 14 Sayı: 1, 169 - 175, 28.03.2024

Duygu Sarı Ak Omar Alomari Ülkan Kılıç

https://doi.org/10.33808/clinexphealthsci.1256952

Öz

Objective: The healthcare system worldwide has faced unparalleled challenges as a result of the coronavirus disease of 2019 (COVID-19) pandemic. While respiratory tract disease is the most common symptom of COVID-19, there is increasing evidence of neurological damage caused by the virus. To guide the clinical management of the disease, it is essential to elucidate the mechanisms underlying the
pathophysiology of COVID-19. Various research indicate that COVID-19 patients exhibit reduced levels of brain-derived neurotrophic factor (BDNF), which is also a hallmark of Huntington’s disease, a neurodegenerative disorder. The objective of this study is to investigate the possible links between COVID-19 and Huntington’s disease. This aim is motivated by the need to guide the clinical management of COVID-19, especially given the increasing evidence of neurological damage caused by the virus, including reduced levels of BDNF, a hallmark also observed in Huntington’s disease.
Methods: The comprehensive literature review conducted for both COVID-19 and Huntington’s disease, focusing on the genes associated with both conditions. These genes were then analyzed using the STRING database to determine protein-protein interactions, aiming to elucidate the mechanisms underlying the pathophysiology of COVID-19 and its potential connections to Huntington’s disease.
Results: The outcomes of the study indicate that there could be molecular-level interactions between COVID-19 and Huntington’s disease, based on the literature research and STRING database analysis. Although the primary mechanism behind these interactions is not yet fully understood, the hypothesis suggests that BDNF and its high-affinity receptor TrkB may play a crucial role. Additionally, the study highlights olfactory dysfunction as a common symptom of COVID-19, which is also linked with various neurodegenerative conditions, including Huntington’s disease.
Conclusion: This work emphasizes the connection between COVID-19 and neurodegenerative diseases, particularly through the lens of olfactory dysfunction, a common symptom shared by COVID-19 and Huntington’s disease. The potential molecular interactions observed suggest that COVID-19 could exacerbate neurodegenerative processes. This underscores the critical need for further research focused on olfactory dysfunction as a key symptom, to better understand and manage the implications of COVID-19 in patients with neurodegenerative conditions.

Anahtar Kelimeler

olfactory dysfunction, amyloid- β, α-synuclein, BDNF, ACE2, NTRK2

Kaynakça

• Mao R, Qiu Y, He JS, Tan JY, Li XH, Liang J, Shen J, Zhu LR, Chen Y, Iacucci M, Ng SC, Ghosh S, Chen MH. Manifestations and prognosis of gastrointestinal and liver involvement in patients with COVID-19: A systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2020;5:667–678. DOI:10.1016/S2468-1253(20)30126-6.
• Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The Lancet. 2020;395:497–506. DOI:10.1016/S0140-6736(20)30183-5.
• Yang L, Liu S, Liu J, Zhang Z, Wan X, Huang B, Chen Y, Zhang Y. COVID-19: immunopathogenesis and Immunotherapeutics. Signal Transduct Target Ther. 2020;5:128. DOI:10.1038/s41392-020-00243-2.
• Ren AL, Digby RJ, Needham EJ. Neurological update: COVID-19. J Neurol. 2021;268:4379–4387. DOI:10.1007/s00415-021-10581-y.
• Zheng JL, Li GZ, Chen SZ, Wang JJ, Olson JE, Xia HJ, Lazartigues E, Zhu Y-L, Chen Y-F. Angiotensin Converting Enzyme 2/Ang-(1-7)/Mas Axis Protects Brain from Ischemic Injury with a Tendency of Age-dependence. CNS Neurosci Ther. 2014;20:452–459. DOI:10.1111/cns.12233.
• Hooper N, Turner A. Protein Processing Mechanisms: From Angiotensin Converting Enzyme to Alzheimer’s Disease. Biochem Soc Trans. 2000;24:441–446.
• Motaghinejad M, Motevalian M, Falak R, Heidari M, Sharzad M, Kalantari E. Neuroprotective effects of various doses of topiramate against methylphenidate-induced oxidative stress and inflammation in isolated rat amygdala: the possible role of CREB/BDNF signaling pathway. J Neural Transm. 2016;123:1463–1477. DOI:10.1007/s00702-016-1619-1.
• Li W, Moore MJ, Vasilieva N, Sui J, Wong SK, Berne MA, Somasundaran M, Sullivan JL, Luzuriaga K, Greenough TC, Choe H, Farzan M. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature. 2003;426:450–454. DOI:10.1038/nature02145.
• Wang XL, Iwanami J, Min LJ, Tsukuda K, Nakaoka H, Bai HY, Shan BS, Kan-no H, Kukida M, Chisaka T, Yamauchi T, Higaki A, Mogi M, Horiuchi M. Deficiency of angiotensin-converting enzyme 2 causes deterioration of cognitive function. NPJ Aging Mech Dis. 2016;2:16024. DOI:10.1038/npjamd.2016.24.
• Verdecchia P, Cavallini C, Spanevello A, Angeli F. The pivotal link between ACE2 deficiency and SARS-CoV-2 infection. Eur J Intern Med. 2020;76:14–20. DOI:10.1016/j.ejim.2020.04.037.
• Azoulay D, Shehadeh M, Chepa S, Shaoul E, Baroum M, Horowitz NA, Kaykov E. Recovery from SARS-CoV-2 infection is associated with serum BDNF restoration. Journal of Infection. 2020;81:e79–81. DOI:10.1016/j.jinf.2020.06.038.
• Cao T, Matyas JJ, Renn CL, Faden AI, Dorsey SG, Wu J. Function and Mechanisms of Truncated BDNF Receptor TrkB.T1 in Neuropathic Pain. Cells. 2020;9:1194. DOI:10.3390/cells9051194.
• Mantilla CB, Greising SM, Stowe JM, Zhan WZ, Sieck GC. TrkB kinase activity is critical for recovery of respiratory function after cervical spinal cord hemisection. Exp Neurol. 2014;261:190–195. DOI:10.1016/j.expneurol.2014.05.027.
• Zuccato C, Cattaneo E. Brain-derived neurotrophic factor in neurodegenerative diseases. Nat Rev Neurol. 2009;5:311–322. DOI:10.1038/nrneurol.2009.54.
• Pivac N, Kozaric-Kovacic D, Grubisic-Ilic M, Nedic G, Rakos I, Nikolac M, Blazev M, Muck-Seler D. The association between brain-derived neurotrophic factor Val66Met variants and psychotic symptoms in posttraumatic stress disorder. The World Journal of Biological Psychiatry. 2012;13:306–311. DOI:10.3109/15622975.2011.582883.
• Pringsheim T, Wiltshire K, Day L, Dykeman J, Steeves T, Jette N. The incidence and prevalence of Huntington’s disease: A systematic review and meta-analysis. Movement Disorders. 2012;27:1083–1091. DOI:10.1002/mds.25075.
• Bates GP, Dorsey R, Gusella JF, Hayden MR, Kay C, Leavitt BR, Nance M, Ross CA, Scahill RI, Wetzel R, Wild EJ, Tabrizi SJ. Huntington disease. Nat Rev Dis Primers. 2015;1:15005. DOI:10.1038/nrdp.2015.5.
• Yu S, Liang Y, Palacino J, Difiglia M, Lu B. Drugging unconventional targets: insights from Huntington’s disease. Trends Pharmacol Sci. 2014;35:53–62. DOI:10.1016/j.tips.2013.12.001.
• Walker FO. Huntington’s disease. The Lancet. 2007;369:218–228. DOI:10.1016/S0140-6736(07)60111-1.
• Zhao X, Chen XQ, Han E, Hu Y, Paik P, Ding Z, Overman J, Lau AL, Shahmoradian SH, Chiu W, Thompson LM, Wu C, Mobley WC. TRiC subunits enhance BDNF axonal transport and rescue striatal atrophy in Huntington’s disease. Proceedings of the National Academy of Sciences. 2016;113. DOI:10.1073/pnas.1603020113.
• Zuccato C, Marullo M, Conforti P, MacDonald ME, Tartari M, Cattaneo E. RESEARCH ARTICLE: Systematic Assessment of BDNF and Its Receptor Levels in Human Cortices Affected by Huntington’s Disease. Brain Pathology. 2007;18:225–238. DOI:10.1111/j.1750-3639.2007.00111.x.
• Victor MB, Richner M, Olsen HE, Lee SW, Monteys AM, Ma C, Huh CJ, Zhang B, Davidson BL, Yang XW, Yoo AS. Striatal neurons directly converted from Huntington’s disease patient fibroblasts recapitulate age-associated disease phenotypes. Nat Neurosci. 2018;21:341–352. DOI:10.1038/s41593-018-0075-7.
• Liot G, Zala D, Pla P, Mottet G, Piel M, Saudou F. Mutant Huntingtin Alters Retrograde Transport of TrkB Receptors in Striatal Dendrites. Journal of Neuroscience. 2013;33:6298–309. DOI:10.1523/JNEUROSCI.2033-12.2013.
• Plotkin JL, Surmeier DJ. Impaired striatal function in Huntington’s disease is due to aberrant p75NTR signaling. Rare Diseases. 2014;2:e968482. DOI:10.4161/2167549X.2014.968482.
• Szklarczyk D, Franceschini A, Wyder S, Forslund K, Heller D, Huerta-Cepas J, Simonovic M, Roth A, Santos A, Tsafou KP, Kuhn M, Bork P, Jensen LJ, von Mering C. STRING v10: protein-protein interaction networks, integrated over the tree of life. Nucleic Acids Res. 2015;43:D447-452. DOI:10.1093/nar/gku1003.
• Doty RL. Olfactory dysfunction in neurodegenerative diseases: is there a common pathological substrate? Lancet Neurol. 2017;16:478–488. DOI:10.1016/S1474-4422(17)30123-0.
• Moein ST, Hashemian SM, Mansourafshar B, Khorram‐Tousi A, Tabarsi P, Doty RL. Smell dysfunction: A biomarker for COVID‐19. Int Forum Allergy Rhinol. 2020;10:944–950. DOI:10.1002/alr.22587.
• Liang F. Sustentacular cell enwrapment of olfactory receptor neuronal dendrites: An update. Genes (Basel). 2020;11:493. DOI:10.3390/genes11050493.
• Glezer I, Bruni‐Cardoso A, Schechtman D, Malnic B. Viral infection and smell loss: The case of COVID‐19. J Neurochem. 2021;157:930–943. DOI:10.1111/jnc.15197.
• Lechien JR, Chiesa-Estomba CM, De Siati DR, Horoi M, Le Bon SD, Rodriguez A, Dequanter D, Blecic S, El Afia F, Distinguin L, Chekkoury-Idrissi Y, Hans S, Delgado IL, Calvo-Henriquez C, Lavigne P, Falanga C, Barillari MR, Cammaroto G, Khalife M, Leich P, Souchay C, Rossi C, Journe F, Hsieh J, Edjlali M, Carlier R, Ris L, Lovato A, De Filippis C, Coppee F, Fakhry N, Ayad T, Saussez S. Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): A multicenter European study. European Archives of Oto-Rhino-Laryngology. 2020;277:2251–2261. DOI:10.1007/s00405-020-05965-1.
• Wu J, Deng W, Li S, Yang X. Advances in research on ACE2 as a receptor for 2019-nCoV. Cellular and Molecular Life Sciences. 2021;78:531–544. DOI:10.1007/s00018-020-03611-x.
• Solomon IH, Normandin E, Bhattacharyya S, Mukerji SS, Keller K, Ali AS, Adams G, Hornick JL, Padera RF, Sabeti P. Neuropathological Features of Covid-19. New England Journal of Medicine. 2020;383:989–992. DOI:10.1056/NEJMc2019373.
• Brann DH, Tsukahara T, Weinreb C, Lipovsek M, Van den Berge K, Gong B, Chance R, Macaulay IC, Chou H-J, Fletcher RB, Das D, Street K, de Bezieux HR, Choi Y-G, Risso D, Dudoit S, Purdom E, Mill J, Hachem RA, Matsunami H, Logan DW, Goldstein BJ, Grubb MS, Ngai J, Datta SR. Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia. Sci Adv. 2020;6. DOI:10.1126/sciadv.abc5801.
• Chen R, Wang K, Yu J, Howard D, French L, Chen Z, Wen C, Xu Z. The Spatial and Cell-Type Distribution of SARS-CoV-2 Receptor ACE2 in the Human and Mouse Brains. Front Neurol. 2021;11. DOI:10.3389/fneur.2020.573095.
• Sardu C, Gambardella J, Morelli MB, Wang X, Marfella R, Santulli G. Hypertension, thrombosis, kidney failure, and diabetes: Is COVID-19 an endothelial disease? A comprehensive evaluation of clinical and basic evidence. J Clin Med. 2020;9:1417. DOI:10.3390/jcm9051417.
• Paniz‐Mondolfi A, Bryce C, Grimes Z, Gordon RE, Reidy J, Lednicky J, Sordillo EM, Fowkes M. Central nervous system involvement by severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2). J Med Virol. 2020;92:699–702. DOI:10.1002/jmv.25915.
• Patra T, Meyer K, Geerling L, Isbell TS, Hoft DF, Brien J, Pinto AK, Ray RB, Ray R. SARS-CoV-2 spike protein promotes IL-6 trans-signaling by activation of angiotensin II receptor signaling in epithelial cells. PLoS Pathog. 2020;16:e1009128. DOI:10.1371/journal.ppat.1009128.
• Copaescu A, Smibert O, Gibson A, Phillips EJ, Trubiano JA. The role of IL-6 and other mediators in the cytokine storm associated with SARS-CoV-2 infection. Journal of Allergy and Clinical Immunology. 2020;146:518-534.e1. DOI:10.1016/j.jaci.2020.07.001.
• Idrees D, Kumar V. SARS-CoV-2 spike protein interactions with amyloidogenic proteins: Potential clues to neurodegeneration. Biochem Biophys Res Commun. 2021;554:94–98. DOI:10.1016/j.bbrc.2021.03.100.
• Tavassoly O, Safavi F, Tavassoly I. Seeding brain protein aggregation by SARS-CoV-2 as a possible long-term complication of COVID-19 infection. ACS Chem Neurosci. 2020;11:3704–3706. DOI:10.1021/acschemneuro.0c00676.
• Lippi A, Domingues R, Setz C, Outeiro TF, Krisko A. SARS‐CoV‐2: At the crossroad between aging and neurodegeneration. Movement Disorders 2020;35:716–720. DOI:10.1002/mds.28084.
• Singh K, Chen Y-C, Hassanzadeh S, Han K, Judy JT, Seifuddin F, Tunc I, Sack MN, Pirooznia M. Network analysis and transcriptome profiling identify autophagic and mitochondrial dysfunctions in SARS-CoV-2 infection. Front Genet. 2021;12. DOI:10.3389/fgene.2021.599261.
• Estrada E. Cascading from SARS-CoV-2 to Parkinson’s Disease through protein-protein interactions. Viruses 2021;13:897. DOI:10.3390/v13050897.
• Ramani A, Müller L, Ostermann PN, Gabriel E, Abida‐Islam P, Müller‐Schiffmann A, Mariappan A, Goureau O, Gruell H, Walker A, Andrée M, Hauka S, Houwaart T, Dilthey A, Wohlgemuth K, Omran H, Klein F, Wieczorek D, Adams O, Timm J, Korth C, Schaal H, Gopalakrishnan J. SARS ‐CoV‐2 targets neurons of 3D human brain organoids. EMBO J. 2020;39. DOI:10.15252/embj.2020106230.
• Busse LW, Chow JH, McCurdy MT, Khanna AK. COVID-19 and the RAAS—A potential role for angiotensin II? Crit Care. 2020;24:136. DOI:10.1186/s13054-020-02862-1.
• Zuccato C, Cattaneo E. Role of brain-derived neurotrophic factor in Huntington’s disease. Prog Neurobiol. 2007;81:294–330. DOI:10.1016/j.pneurobio.2007.01.003.
• Gauthier LR, Charrin BC, Borrell-Pagès M, Dompierre JP, Rangone H, Cordelières FP, De Mey J, MacDonald ME, Leßmann V, Humbert S, Saudou F. Huntingtin controls neurotrophic support and survival of neurons by enhancing BDNF vesicular transport along microtubules. Cell 2004;118:127–138. DOI:10.1016/j.cell.2004.06.018.
• Ciarochi J, Liu J, Calhoun V, Johnson H, Misiura M, Bockholt H, Espinoza F, Caprihan A, Plis S, Turner J, Paulsen J. High and low levels of an NTRK2-driven genetic profile affect motor- and cognition-associated Frontal Gray Matter in Prodromal Huntington’s Disease. Brain Sci. 2018;8:116. DOI:10.3390/brainsci8070116.
• Wang L, de Kloet AD, Pati D, Hiller H, Smith JA, Pioquinto DJ, Ludin JA, Oh SP, Katovich MJ, Frazier CJ, Raizada MK, Krause EG. Increasing brain angiotensin converting enzyme 2 activity decreases anxiety-like behavior in male mice by activating central Mas receptors. Neuropharmacology 2016;105:114–123. DOI:10.1016/j.neuropharm.2015.12.026.
• Mowla SJ, Farhadi HF, Pareek S, Atwal JK, Morris SJ, Seidah NG, Murphy RA. Biosynthesis and post-translational processing of the precursor to brain-derived neurotrophic factor. Journal of Biological Chemistry 2001;276:12660–12666. DOI:10.1074/jbc.M008104200.