Clozapine-N-oxide protects dopaminergic neurons against rotenone-induced neurotoxicity by preventing ferritinophagy-mediated ferroptosis.

ABSTRACT: Parkinson's disease (PD) is the second most common neurodegenerative disorder, yet treatment options are limited. Clozapine (CLZ), an antipsychotic used for schizophrenia, has potential as a PD treatment. CLZ and its metabolite, Clozapine-N-Oxide (CNO), show neuroprotective effects on dopaminergic neurons, with mechanisms needing further investigation. This study aimed to confirm the neuroprotective effects of CLZ and CNO in a rotenone-induced mouse model and further explore the underlying mechanisms of CNO-afforded protection. Gait pattern and rotarod activity evaluations showed motor impairments in rotenone-exposed mice, with CLZ or CNO administration ameliorating behavioral deficits. Cell counts and biochemical analysis demonstrated CLZ and CNO's effectiveness in reducing rotenone-induc

SUBMITTER: Sun Q 

PROVIDER: S-EPMC10842931 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature