Alpha-synuclein overexpression triggers divergent cellular responses and post-translational modifications in SH-SY5Y and ReNcell VM models.

ABSTRACT: Alpha‑synuclein (α‑syn) overexpression models are widely used to unravel the molecular mechanisms of Parkinson's disease (PD), particularly in light of the dose-dependent transition between its physiological and toxic roles. However, existing systems rely on inducible expression, lack robust dose stratification and comparative cellular contexts. Here, we developed and characterized a panel of stable neuronal cell lines in two human cellular models (SH‑SY5Y neuroblastoma cells and ReNcell VM neural progenitors) overexpressing GFP-tagged wild-type (WT) or A53T mutant α‑syn at low and high overexpression levels. Utilizing this framework, we demonstrated that A53T consistently induces cytotoxicity, oxidative stress and mitochondrial dysfunction in both cell types. In contrast, WT α‑syn had div

SUBMITTER: Momand MUD 

PROVIDER: S-EPMC12932749 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature