The biphasic role of Hspb1 on ferroptotic cell death in Parkinson's disease.

ABSTRACT: Rationale: Ferroptosis-driven loss of dopaminergic neurons plays a pivotal role in the pathogenesis of Parkinson's disease (PD). In PD patients, Hspb1 is commonly observed at abnormally high levels in the substantia nigra. The precise consequences of Hspb1 overexpression in PD, however, have yet to be fully elucidated. Methods: We used human iPSC-derived dopaminergic neurons and Coniferaldehyde (CFA)-an Nrf2 agonist known for its ability to cross the blood-brain barrier-to investigate the role of Hspb1 in PD. We examined the correlation between Hspb1 overexpression and Nrf2 activation and explored the transcriptional regulation of Hspb1 by Nrf2. Gene deletion techniques were employed to determine the necessity of Nrf2 and Hspb1 for CFA's neuroprotective effects. Results

SUBMITTER: Meng J 

PROVIDER: S-EPMC11373631 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature