The role of alpha-synuclein in synucleinopathy: Impact on lipid regulation at mitochondria-ER membranes.

ABSTRACT: The protein alpha-synuclein (αSyn) plays a pivotal role in the pathogenesis of synucleinopathies, including Parkinson's disease and multiple system atrophy, with growing evidence indicating that lipid dyshomeostasis is a key phenotype in these neurodegenerative disorders. Previously, we identified that αSyn localizes, at least in part, to mitochondria-associated endoplasmic reticulum membranes (MAMs), which are transient functional domains containing proteins that regulate lipid metabolism, including the de novo synthesis of phosphatidylserine. In the present study, we analyzed the lipid composition of postmortem human samples, focusing on the substantia nigra pars compacta of Parkinson's disease and controls, as well as three less affected brain regions of Parkinson's donors. To further a

SUBMITTER: Barbuti PA 

PROVIDER: S-EPMC12043847 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature