Motor and non-motor circuit disturbances in early Parkinson disease: which happens first?

Animals Efferent Pathways / physiopathology Humans Neural Pathways / physiopathology Parkinson Disease / genetics alpha-Synuclein / genetics

Journal

Nature reviews. Neuroscience
ISSN: 1471-0048
Titre abrégé: Nat Rev Neurosci
Pays: England
ID NLM: 100962781

Informations de publication

Date de publication:
02 2022
Historique:
accepted: 12 11 2021
pubmed: 16 12 2021
medline: 26 2 2022
entrez: 15 12 2021
Statut: ppublish

Résumé

For the last two decades, pathogenic concepts in Parkinson disease (PD) have revolved around the toxicity and spread of α-synuclein. Thus, α-synuclein would follow caudo-rostral propagation from the periphery to the central nervous system, first producing non-motor manifestations (such as constipation, sleep disorders and hyposmia), and subsequently impinging upon the mesencephalon to account for the cardinal motor features before reaching the neocortex as the disease evolves towards dementia. This model is the prevailing theory of the principal neurobiological mechanism of disease. Here, we scrutinize the temporal evolution of motor and non-motor manifestations in PD and suggest that, even though the postulated bottom-up mechanisms are likely to be involved, early involvement of the nigrostriatal system is a key and prominent pathophysiological mechanism. Upcoming studies of detailed clinical manifestations with newer neuroimaging techniques will allow us to more closely define, in vivo, the role of α-synuclein aggregates with respect to neuronal loss during the onset and progression of PD.

Identifiants

DOI: 10.1038/s41583-021-00542-9 PMID: 34907352
pubmed: 34907352
doi: 10.1038/s41583-021-00542-9
pii: 10.1038/s41583-021-00542-9
doi:

Substances chimiques

SNCA protein, human 0
alpha-Synuclein 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

115-128

Informations de copyright

© 2021. Springer Nature Limited.

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Auteurs

Javier Blesa (J)

HM CINAC (Centro Integral de Neurociencias Abarca Campal), Hospital Universitario HM Puerta del Sur, HM Hospitales, Madrid, Spain.
Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED), Instituto Carlos III, Madrid, Spain.
ORCID: 0000-0002-4257-1325

Guglielmo Foffani (G)

HM CINAC (Centro Integral de Neurociencias Abarca Campal), Hospital Universitario HM Puerta del Sur, HM Hospitales, Madrid, Spain.
Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED), Instituto Carlos III, Madrid, Spain.
Hospital Nacional de Parapléjicos, SESCAM, Toledo, Spain.

Benjamin Dehay (B)

Univ. Bordeaux, CNRS, IMN, UMR 5293, Bordeaux, France.
ORCID: 0000-0003-1723-9045

Erwan Bezard (E)

Univ. Bordeaux, CNRS, IMN, UMR 5293, Bordeaux, France.
ORCID: 0000-0002-0410-4638

Jose A Obeso (JA)

HM CINAC (Centro Integral de Neurociencias Abarca Campal), Hospital Universitario HM Puerta del Sur, HM Hospitales, Madrid, Spain. jobeso.hmcinac@hmhospitales.com.
Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED), Instituto Carlos III, Madrid, Spain. jobeso.hmcinac@hmhospitales.com.
University CEU-San Pablo, Madrid, Spain. jobeso.hmcinac@hmhospitales.com.
ORCID: 0000-0002-6996-8613

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Motor and non-motor circuit disturbances in...
questionsmedicales.fr › Système nerveux › Voies nerveuses › Voies efférentes › Motor and non-motor circuit disturbances in...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Motor and non-motor circuit disturbances in...
questionsmedicales.fr › Système nerveux › Voies nerveuses › Motor and non-motor circuit disturbances in...
questionsmedicales.fr › Maladies du système nerveux › Maladies neurodégénératives › Maladie de Parkinson › Motor and non-motor circuit disturbances in...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines associées à la maladie de Parkinson › alpha-Synucléine › Motor and non-motor circuit disturbances in...