Contrasting Effects of Clozapine and Risperidone on Cholesterol Metabolism, Synaptic Proteins, and Transcriptional Regulation in Human LUHMES Neurons.

ABSTRACT: Antipsychotic drugs elicit complex cellular responses in neurons, yet the molecular mechanisms underlying their actions remain incompletely understood. Here, we employed deep proteomic profiling (DDA/DIA-MS) in LUHMES-derived dopaminergic neurons to explore the distinct proteomic profile induced by clozapine and risperidone. Pathway analysis revealed that clozapine robustly upregulated lipid metabolic pathways, particularly those involved in cholesterol and fatty acid biosynthesis. Conversely, risperidone primarily enhanced oxidative phosphorylation and modulated synaptic architecture and protein metabolic-pathways. Functional enrichment further indicated that clozapine promotes sterol metabolism, neuronal viability, and neurite outgrowth-hallmarks of neurotrophic activity - while simultan

SUBMITTER: Rybczynski P 

PROVIDER: S-EPMC12657556 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature