Mycobacterial immunomodulation and viral manipulation of neuronal copper efflux in the setting of sporadic Parkinson's disease: A multi – hit, outside – in hypothesis of its pathogenesis
dc.creator | Vavougios G.D. | en |
dc.date.accessioned | 2023-01-31T10:30:19Z | |
dc.date.available | 2023-01-31T10:30:19Z | |
dc.date.issued | 2020 | |
dc.identifier | 10.1016/j.mehy.2019.109505 | |
dc.identifier.issn | 03069877 | |
dc.identifier.uri | http://hdl.handle.net/11615/80528 | |
dc.description.abstract | Following Braak's hypothesis on the infectious pathogenesis of sporadic Parkinson's disease (sPD), several bacteria and viruses have been investigated as likely culprits. Recent research has focused on neuroinvasive influenza A viruses (IAV), whereas a genetic link between sPD and tuberculosis has arisen in LRRK2 – dependent maturation of the phagosome. An integrative, outside – in, multi – hit hypothesis is presented here, where (a) mycobacterial immunomodulation creates a phagocyte niche along with cytokine mediated, site specific (i.e. the gut) alterations of both immunity and the microbiome, (b) copper modulating IAVs gain latency in and control over phagocytes and their phenotypes, (c) gain access to the central nervous system (CNS) via the olfactory and vagus nerves in subsequent infection cycles, (d) induce indolent neuroinflammation characterized by perturbed intraneuronal copper compartmentalization and (e) produce α – synuclein (aSyn) pathology at least in part via copper – induced aggregation and misfolding as well as potential synergy with other underlying, corroborating factors (either genetic or acquired) contributing to dopaminergic neurodegeneration. This hypothesis explores recently arisen evidence for each step of this process, as well as pre-existing, yet unexplored overlapping pathophysiological characteristics of sPD with mycobacterial and IAV infections. The implications of this proposed pathogenic model extend both in sPD research (i.e. determining non – tuberculous mycobacteria as the first hit organism, inactivating IAV – induced copper hijacking), as well as therapeutics. © 2019 Elsevier Ltd | en |
dc.language.iso | en | en |
dc.source | Medical Hypotheses | en |
dc.source.uri | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85075213351&doi=10.1016%2fj.mehy.2019.109505&partnerID=40&md5=ce10646bf7b3b92bfa9eb67630477d71 | |
dc.subject | copper | en |
dc.subject | DNA | en |
dc.subject | alpha synuclein | en |
dc.subject | copper | en |
dc.subject | Article | en |
dc.subject | cation transport | en |
dc.subject | cell compartmentalization | en |
dc.subject | copper efflux | en |
dc.subject | copper metabolism | en |
dc.subject | DNA modification | en |
dc.subject | epigenetics | en |
dc.subject | homeostasis | en |
dc.subject | host pathogen interaction | en |
dc.subject | human | en |
dc.subject | immunomodulation | en |
dc.subject | Influenza A virus | en |
dc.subject | macrophage | en |
dc.subject | Mycobacterium | en |
dc.subject | nerve cell | en |
dc.subject | nerve degeneration | en |
dc.subject | nonhuman | en |
dc.subject | Parkinson disease | en |
dc.subject | pathogenesis | en |
dc.subject | phenotype | en |
dc.subject | sporadic Parkinson disease | en |
dc.subject | virus latency | en |
dc.subject | central nervous system | en |
dc.subject | endoplasmic reticulum stress | en |
dc.subject | genetic epigenesis | en |
dc.subject | immunology | en |
dc.subject | metabolism | en |
dc.subject | microbiology | en |
dc.subject | mycobacteriosis | en |
dc.subject | Mycobacterium | en |
dc.subject | nerve cell | en |
dc.subject | oxidative stress | en |
dc.subject | Parkinson disease | en |
dc.subject | theoretical model | en |
dc.subject | virology | en |
dc.subject | virus infection | en |
dc.subject | alpha-Synuclein | en |
dc.subject | Central Nervous System | en |
dc.subject | Copper | en |
dc.subject | Endoplasmic Reticulum Stress | en |
dc.subject | Epigenesis, Genetic | en |
dc.subject | Humans | en |
dc.subject | Immunomodulation | en |
dc.subject | Models, Theoretical | en |
dc.subject | Mycobacterium | en |
dc.subject | Mycobacterium Infections | en |
dc.subject | Neurons | en |
dc.subject | Oxidative Stress | en |
dc.subject | Parkinson Disease | en |
dc.subject | Phenotype | en |
dc.subject | Virus Diseases | en |
dc.subject | Churchill Livingstone | en |
dc.title | Mycobacterial immunomodulation and viral manipulation of neuronal copper efflux in the setting of sporadic Parkinson's disease: A multi – hit, outside – in hypothesis of its pathogenesis | en |
dc.type | journalArticle | en |
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