The heterogeneity of Parkinson’s disease

Ullrich Wüllner*, Per Borghammer, Chi un Choe, Ilona Csoti, Björn Falkenburger, Thomas Gasser, Paul Lingor, Peter Riederer

*Kontaktforfatter

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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Abstract

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.

OriginalsprogEngelsk
TidsskriftJournal of Neural Transmission
Vol/bind130
Udgave nummer6
Sider (fra-til)827-838
ISSN0300-9564
DOI
StatusUdgivet - jun. 2023

Bibliografisk note

Funding Information:
Support for the German PD Expert meeting 2022 from Bial, Desitin Arzneimittel GmbH and Zambon GmbH is gratefully acknowledged.

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