Atsushi Sato Pages 533 - 543 ( 11 )
Mammalian target of rapamycin (mTOR) is a key regulator in various cellular processes, including cell growth, gene expression, and synaptic functions. Autism spectrum disorder (ASD) is frequently accompanied by monogenic disorders, such as tuberous sclerosis complex, phosphatase and tensin homolog tumor hamartoma syndrome, neurofibromatosis 1, and fragile X syndrome, in which mTOR is hyperactive. Mutations in the genes involved in the mTOR-mediated signaling pathway have been identified in some cases of syndromic ASD. Evidences indicate a pathogenic role for hyperactive mTOR-mediated signaling in ASD associated with these monogenic disorders, and mTOR inhibitors are a potential pharmacotherapy for ASD. Abnormal synaptic transmission through metabotropic glutamate receptor 5 may underlie in a part of ASD associated with hyperactive mTOR-mediated signaling. In this review, the relationship between mTOR and ASD is discussed.
Autophagy, fragile X syndrome, mammalian target of rapamycin, metabotropic glutamate receptor 5, neurofibromatosis, phosphatase and tensin homolog, tuberous sclerosis complex
Department of Pediatrics, The University of Tokyo Hospital, Addictive Substance Project, Tokyo Metropolitan Institute of Medical Science, Hongo 7-3-1, Bunkyo-ku, Tokyo, 113- 8655, Japan.