Abnormal α-synuclein binds to synaptotagmin 13, impairing extracellular vesicle release in synucleinopathies.

ABSTRACT:

Background

Despite increasing in vitro research, direct evidence of how abnormal α-synuclein (α-Syn) dysregulates vesicular transport and synaptic function in the human brain is lacking.

Methods

We performed a transcriptome analysis using brain tissues from a multiple system atrophy (MSA) mouse model, which develops human α-Syn-positive glial cytoplasmic inclusion-like structures and neuronal cytoplasmic inclusion-like structures after tamoxifen injection. We then performed histologic and biochemical analyses using brain samples from 71 human cases (Parkinson's disease, n = 10; dementia with Lewy bodies [DLB], n = 19; MSA, n = 15; control: n = 27), a human blood sample (control: n = 1), and cultured cells.

Results

Based on the transcriptome of the MSA mouse model, we

SUBMITTER: Miki Y 

PROVIDER: S-EPMC12183919 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature