Tag: mTOR

Autophagy pathway alterations in lymphocytes: Potential biomarkers for autism?

Components of the mammalian target of rapamycin (mTOR) signaling pathway are key players in the pathogenesis of autism spectrum disorder (ASD). The mTOR pathway regulates protein homeostasis by promoting protein synthesis and inhibiting autophagy, a lysosomal degradation process that maintains protein quality control by breaking down cellular proteins and organelles to generate amino acids. Guomei Tang, David Sulzer and their colleagues at Columbia University Medical Center recently analyzed postmortem brain samples from individuals with ASD and discovered that, in response to hyperactive mTOR, autophagy was impaired in excitatory neurons[ref]Tang G. et al. Neuron 83, 1131-1143 (2014) PubMed[/ref]. In animal models, autophagy deficiency causes ASD-like synapse pathology and social behaviors.

Genetic rescue of a mouse model of Fragile X by targeted deletion of RICTOR

Fragile X syndrome is the most common heritable form of intellectual disabilities and a leading genetic cause of autism, caused by mutation of the gene encoding FMRP. Researchers have not found an effective treatment for the cognitive and social interaction deficits associated with fragile X. The mammalian target of rapamycin (mTOR) is a central regulator of cell growth, proliferation, survival, translation and the actin cytoskeleton. mTOR is a kinase that integrates external cues and forms two distinct complexes, mTOR Complex 1 (mTORC1) and Complex 2 (mTORC2), which have distinct functions and downstream targets. Whereas mTORC1 is a central regulator of cap-dependent translation, mTORC2 is a pivotal regulator of the actin cytoskeleton, spine structure and memory. Dysregulation of mTORC1 in fragile X syndrome is well established, but a role for mTORC2 is still unclear.

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