ZSCAN21 mediates the pathogenic transcriptional induction of α-synuclein in cellular and animal models of Parkinson's disease.

ABSTRACT: The expression level of α-synuclein is thought to play a crucial role in the pathogenesis of Parkinson's disease. However, little is known about the molecular mechanisms regulating the transcription of its gene, SNCA, particularly in the context of the disease. The transcription factor ZSCAN21 has been shown to act on SNCA, but whether ZSCAN21 is actually involved in the induction of SNCA transcription in Parkinson's disease is unknown. To address this question, we used the MPTP mouse model and LUHMES-derived dopaminergic neuronal spheroids, subjected to Parkinson's disease-related neurotoxins and mutations. We show that MPP⁺-treated spheroids recapitulate the main features of α-synuclein pathology and that MPP⁺-triggered transcriptional induction of SNCA is associate

SUBMITTER: Kozoriz A 

PROVIDER: S-EPMC12084422 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature