Pathophysiological evaluation of the LRRK2 G2385R risk variant for Parkinson's disease.
Journal
NPJ Parkinson's disease
ISSN: 2373-8057
Titre abrégé: NPJ Parkinsons Dis
Pays: United States
ID NLM: 101675390
Informations de publication
Date de publication:
05 Aug 2022
05 Aug 2022
Historique:
received:
06
05
2022
accepted:
20
07
2022
entrez:
5
8
2022
pubmed:
6
8
2022
medline:
6
8
2022
Statut:
epublish
Résumé
Missense variants in leucine-rich repeat kinase 2 (LRRK2) lead to familial and sporadic Parkinson's disease (PD). The pathological features of PD patients with LRRK2 variants differ. Here, we report an autopsy case harboring the LRRK2 G2385R, a risk variant for PD occurring mainly in Asian populations. The patient exhibited levodopa-responsive parkinsonism at the early stage and visual hallucinations at the advanced stage. The pathological study revealed diffuse Lewy bodies with neurofibrillary tangles, amyloid plaques, and mild signs of neuroinflammation. Biochemically, detergent-insoluble phospho-α-synuclein was accumulated in the frontal, temporal, entorhinal cortexes, and putamen, consistent with the pathological observations. Elevated phosphorylation of Rab10, a substrate of LRRK2, was also prominent in various brain regions. In conclusion, G2385R appears to increase LRRK2 kinase activity in the human brain, inducing a deleterious brain environment that causes Lewy body pathology.
Identifiants
pubmed: 35931783
doi: 10.1038/s41531-022-00367-y
pii: 10.1038/s41531-022-00367-y
pmc: PMC9355991
doi:
Types de publication
Journal Article
Langues
eng
Pagination
97Subventions
Organisme : MEXT | Japan Society for the Promotion of Science (JSPS)
ID : 20H03453
Organisme : MEXT | Japan Society for the Promotion of Science (JSPS)
ID : 20K21531
Organisme : Takeda Science Foundation
ID : NA
Organisme : Otsuka Pharmaceutical (Otsuka Pharmaceutical Co., Ltd.)
ID : NA
Organisme : Otsuka Pharmaceutical (Otsuka Pharmaceutical Co., Ltd.)
ID : NA
Organisme : AbbVie (AbbVie Inc.)
ID : NA
Organisme : AbbVie (AbbVie Inc.)
ID : NA
Informations de copyright
© 2022. The Author(s).
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