Preclinical studies and transcriptome analysis in a model of Parkinson's disease with dopaminergic ZNF746 expression.

ABSTRACT:

Background

The parkin-interacting substrate (PARIS, also known as ZNF746) is a transcriptional repressor, whose accumulation and phosphorylation play central pathological roles in Parkinson's disease (PD). PARIS-induced transcriptional repression of PGC-1α or MDM4 contributes to mitochondrial dysfunction and p53-dependent neuron loss in PD. Despite the important role of PARIS in PD pathogenesis, unbiased transcriptomic profiles influenced by PARIS accumulation in dopaminergic neurons remain unexplored.

Methods

We engineered Tet-Off conditional transgenic mice expressing PARIS in dopaminergic neurons, driven by DAT-PF-tTA driver mice. The conditional PARIS transgenic mice were characterized by PD-associated pathologies, including progressive dopamine cell loss, neuroinflammat

SUBMITTER: Kim JH 

PROVIDER: S-EPMC11871723 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature