The heterogeneity of Parkinson's disease.
Disease mechanism
Inflammation
Parkinson’s disease
Pathophysiology
Personalized medicine
Phenotypes
Journal
Journal of neural transmission (Vienna, Austria : 1996)
ISSN: 1435-1463
Titre abrégé: J Neural Transm (Vienna)
Pays: Austria
ID NLM: 9702341
Informations de publication
Date de publication:
06 2023
06 2023
Historique:
received:
20
03
2023
accepted:
12
04
2023
medline:
22
5
2023
pubmed:
12
5
2023
entrez:
11
5
2023
Statut:
ppublish
Résumé
The heterogeneity of Parkinson's disease (PD), i.e. the various clinical phenotypes, pathological findings, genetic predispositions and probably also the various implicated pathophysiological pathways pose a major challenge for future research projects and therapeutic trail design. We outline several pathophysiological concepts, pathways and mechanisms, including the presumed roles of α-synuclein misfolding and aggregation, Lewy bodies, oxidative stress, iron and melanin, deficient autophagy processes, insulin and incretin signaling, T-cell autoimmunity, the gut-brain axis and the evidence that microbial (viral) agents may induce molecular hallmarks of neurodegeneration. The hypothesis is discussed, whether PD might indeed be triggered by exogenous (infectious) agents in susceptible individuals upon entry via the olfactory bulb (brain first) or the gut (body-first), which would support the idea that disease mechanisms may change over time. The unresolved heterogeneity of PD may have contributed to the failure of past clinical trials, which attempted to slow the course of PD. We thus conclude that PD patients need personalized therapeutic approaches tailored to specific phenomenological and etiologic subtypes of disease.
Identifiants
pubmed: 37169935
doi: 10.1007/s00702-023-02635-4
pii: 10.1007/s00702-023-02635-4
pmc: PMC10174621
doi:
Substances chimiques
alpha-Synuclein
0
Types de publication
Journal Article
Review
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
827-838Informations de copyright
© 2023. The Author(s).
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