Angiotensin type 1 receptor activation promotes neuronal and glial alpha-synuclein aggregation and transmission.
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:
17 Feb 2024
17 Feb 2024
Historique:
received:
28
06
2023
accepted:
02
02
2024
medline:
18
2
2024
pubmed:
18
2
2024
entrez:
17
2
2024
Statut:
epublish
Résumé
The brain renin-angiotensin system (RAS) has been related to dopaminergic degeneration, and high expression of the angiotensin II (AngII) type 1 receptor (AT1) gene is a marker of the most vulnerable neurons in humans. However, it is unknown whether AngII/AT1 overactivation affects α-synuclein aggregation and transmission. In vitro, AngII/AT1 activation increased α-synuclein aggregation in dopaminergic neurons and microglial cells, which was related to AngII-induced NADPH-oxidase activation and intracellular calcium raising. In mice, AngII/AT1 activation was involved in MPTP-induced increase in α-synuclein expression and aggregation, as they significantly decreased in mice treated with the AT1 blocker telmisartan and AT1 knockout mice. Cell co-cultures (transwells) revealed strong transmission of α-synuclein from dopaminergic neurons to astrocytes and microglia. AngII induced a higher α-synuclein uptake by microglial cells and an increase in the transfer of α-synuclein among astroglial cells. However, AngII did not increase the release of α-synuclein by neurons. The results further support brain RAS dysregulation as a major mechanism for the progression of Parkinson's disease, and AT1 inhibition and RAS modulation as therapeutic targets.
Identifiants
pubmed: 38368444
doi: 10.1038/s41531-024-00650-0
pii: 10.1038/s41531-024-00650-0
doi:
Types de publication
Journal Article
Langues
eng
Pagination
37Subventions
Organisme : Ministerio de Economía y Competitividad (Ministry of Economy and Competitiveness)
ID : PID2021-126848NB-I00
Organisme : Ministerio de Economía y Competitividad (Ministry of Economy and Competitiveness)
ID : PLEC2022-009401
Organisme : Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III)
ID : RD21/0017/0031
Organisme : Consellería de Cultura, Educación e Ordenación Universitaria, Xunta de Galicia (Ministry of Culture, Education and University Planning, Government of Galicia)
ID : ED431C 2022/41
Informations de copyright
© 2024. The Author(s).
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