Synaptic vesicle-omics in mice captures signatures of aging and synucleinopathy.

ABSTRACT: Neurotransmitter release occurs through exocytosis of synaptic vesicles. α-Synuclein's function and dysfunction in Parkinson's disease and other synucleinopathies is thought to be tightly linked to synaptic vesicle binding. Age is the biggest risk factor for synucleinopathy, and ~15% of synaptic vesicle proteins have been linked to central nervous system diseases. Yet, age- and disease-induced changes in synaptic vesicles remain unexplored. Via systematic analysis of synaptic vesicles at the ultrastructural, protein, and lipid levels, we reveal specific changes in synaptic vesicle populations, proteins, and lipids over age in wild-type mice and in α-synuclein knockout mice with and without expression of human α-synuclein. Strikingly, we find several previously undescribed synaptic changes

SUBMITTER: Gao V 

PROVIDER: S-EPMC12046008 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature