The Convergence of Two Signaling Pathways Within the Striatum Reveals Potential Mechanisms of Neuropsychiatric Disease

Abstract

The serine-threonine kinase mTOR (mechanistic target of rapamycin) is the cornerstone of a signaling pathway that serves as an essential regulator of cellular processes such as protein synthesis and autophagy (1). Aberrant activity of mTOR complex 1 (mTORC1) has been identified both in neurodevelopmental disorders and in sporadic neurodegenerative disease (2). In particular, loss-of-function mutations in genes encoding negative regulators of mTORC1, such as TSC1, TSC2, and PTEN, result in syndromic neurodevelopmental disorders associated with a constellation of manifestations, which can include epilepsy, autism spectrum disorder, and cognitive impairments.