The transcriptomic signature of DEPDC5 KO induced mTOR hyperactivation in human neurons and its response to rapamycin treatment.

ABSTRACT:

Objective

Mutations of the DEP Domain Containing 5 gene (DEPDC5), a mechanistic Target of Rapamycin (mTOR) inhibitor involved in amino acid sensing, are associated with neurological diseases such as epilepsy and/or autism spectrum disorder (ASD). Loss of DEPDC5 impacts early neuronal development via mTOR hyperactivity. Although, in the mTOR-hyperactivity-associated syndrome tuberous sclerosis, mTOR inhibitors have proven to be beneficial in treating epilepsy, ASD-associated symptoms are ameliorated only partially. Similarly, the mTOR inhibitor rapamycin (RAPA) only partially rescues phenotypes induced by loss of DEPDC5 in animal models, suggesting some pathological mechanisms independent of mTOR.

Methods

We dissected these mechanisms by identifying the DEPDC5-associated gene

SUBMITTER: Jones MSO 

PROVIDER: S-EPMC12661282 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature