title: Plasticity and mTOR: towards restoration of impaired synaptic plasticity in mTOR-related neurogenetic disorders.
abstract: OBJECTIVE
  To review the recent literature on the clinical features, genetic mutations, neurobiology associated with dysregulation of mTOR (mammalian target of rapamycin), and clinical trials for tuberous sclerosis complex (TSC), neurofibromatosis-1 (NF1) and fragile X syndrome (FXS), and phosphatase and tensin homolog hamartoma syndromes (PTHS), which are neurogenetic disorders associated with abnormalities in synaptic plasticity and mTOR signaling.
  
  
  METHODS
  Pubmed and Clinicaltrials.gov were searched using specific search strategies.
  
  
  CONCLUSIONS
  Although traditionally thought of as irreversible disorders, significant scientific progress has been made in both humans and preclinical models to understand how pathologic features of these neurogenetic disorders can be reduced or reversed. This paper revealed significant similarities among the conditions. Not only do they share features of impaired synaptic plasticity and dysregulation of mTOR, but they also share clinical features--autism, intellectual disability, cutaneous lesions, and tumors. Although scientific advances towards discovery of effective treatment in some disorders have outpaced others, progress in understanding the signaling pathways that connect the entire group indicates that the lesser known disorders will become treatable as well.
authors.affiliation: Tuberous Sclerosis Center, Hugo Moser Research Institute, Kennedy Krieger Institute, Baltimore, MD 21205, USA. gipson@kennedykrieger.org
authors.forename: Tanjala T
authors.initials: TT
authors.lastname: Gipson
authors.forename: Michael V
authors.initials: MV
authors.lastname: Johnston
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic / Q000639:trends; D006801:Humans; D009154:Mutation / Q000235:genetics; D009415:Nerve Net / Q000503:physiopathology; D009422:Nervous System Diseases / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy*; D009473:Neuronal Plasticity / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D013569:Synapses / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*
chemical_list: C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases