Dysregulation of protein degradation and alteration of secretome in α-synuclein-exposed astrocytes: implications for dopaminergic neuronal dysfunction.

ABSTRACT:

Background

A key factor in the propagation of α-synuclein pathology is the compromised protein quality control system. Variations in membrane association and astrocytic uptake between different α-synuclein forms suggest differences in exocytosis or membrane cleavage, potentially impacting the secretome's influence on dopaminergic neurons. We aimed to understand differences in protein degradation mechanisms of astrocytes for both wild-type (WT) and mutant forms of α-synuclein, specifically during periods of reduced degradation efficiency. We also investigated α-synuclein release into the secretome and its effects on healthy dopaminergic neurons.

Methods

Cellular models used were rat primary astrocytes alongside hiPSC-derived astrocytes, whose impact on rat primary dopaminergi

SUBMITTER: Raj A 

PROVIDER: S-EPMC11610152 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature