Alpha-Synuclein Phosphomimetic Y39E and S129D Knock-In Mice Show Cytosolic Alpha-Synuclein Localization without Developing Neurodegeneration or Motor Deficits.

ABSTRACT: Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by motor and nonmotor symptoms. Its pathological hallmarks include the accumulation of misfolded alpha-synuclein (α-Syn) in Lewy bodies and Lewy neurites. Phosphorylation of α-Syn is a prominent feature of these inclusions, but its role in disease pathogenesis remains unclear. To identify the role of α-Syn phosphorylation in synucleinopathy, we generated two Snca knock-in (KI) mouse models carrying phosphomimetic mutations at SncaY39 or SncaS129 (Snca^Y39E or Snca^S129D ) which manipulated epitopes phosphorylated in the PD brain. Both Snca^Y39E and Snca^S129D KI mice displayed increased α-Syn phosphorylation, enhanced oligomer formati

SUBMITTER: Kim Y 

PROVIDER: S-EPMC11998964 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature