A stem cell-based assay platform demonstrates alpha-synuclein dependent synaptic dysfunction in patient-derived cortical neurons.
NPJ Parkinsons Dis
; 10(1): 107, 2024 May 21.
Article
em En
| MEDLINE
| ID: mdl-38773105
ABSTRACT
Alpha-synuclein (αS)-rich Lewy bodies and neurites in the cerebral cortex correlate with the presence of dementia in Parkinson disease (PD) and Dementia with Lewy bodies (DLB), but whether αS influences synaptic vesicle dynamics in human cortical neurons is unknown. Using a new iPSC-based assay platform for measuring synaptic vesicle cycling, we found that in human cortical glutamatergic neurons, increased αS from either transgenic expression or triplication of the endogenous locus in patient-derived neurons reduced synaptic vesicle cycling under both stimulated and spontaneous conditions. Thus, using a robust, easily adopted assay platform, we show for the first time αS-induced synaptic dysfunction in human cortical neurons, a key cellular substrate for PD dementia and DLB.
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1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
NPJ Parkinsons Dis
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos