SCD Inhibition Protects from α-Synuclein-Induced Neurotoxicity But Is Toxic to Early Neuron Cultures.

ABSTRACT: Here, we report the independent discovery and validation of stearoyl-CoA desaturase (SCD) as a modulator of α-synuclein (αSyn)-induced pathology and toxicity in cell-based Parkinson's disease (PD) models. We identified SCD as top altered gene from transcriptional profiling in primary neurons exogenously expressing αSyn with the amplified familial PD mutation 3K. Thus, we sought to further explore SCD as a therapeutic target in neurodegeneration. We report that SCD inhibitors are toxic to early human and rat neuron cultures while displaying minimal toxicity to late cultures. The fatty acid product of SCD, oleic acid (OLA), fully rescues this toxicity in early cultures, suggesting on-target toxicity. Furthermore, SCD inhibition rescues αSyn 3K-induced toxicity in late primary neurons. We als

SUBMITTER: Nicholatos JW 

PROVIDER: S-EPMC8387157 | biostudies-literature | 2021 Jul-Aug

REPOSITORIES: biostudies-literature