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Int J Mol Sci. 2018 Jul 30;19(8). pii: E2226. doi: 10.3390/ijms19082226.

mTOR-Related Brain Dysfunctions in Neuropsychiatric Disorders.

Author information

1
Human Anatomy, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Roma 55, 56126 Pisa, Italy. larisa.ryskalin@unipi.it.
2
Human Anatomy, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Roma 55, 56126 Pisa, Italy. f.limanaqi@studenti.unipi.it.
3
I.R.C.C.S. Neuromed, Via Atinense 18, 86077 Isernia, Italy. alessandro.frati@uniroma1.it.
4
I.R.C.C.S. Neuromed, Via Atinense 18, 86077 Isernia, Italy. clbusceti@libero.it.
5
Human Anatomy, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Roma 55, 56126 Pisa, Italy. francesco.fornai@med.unipi.it.
6
I.R.C.C.S. Neuromed, Via Atinense 18, 86077 Isernia, Italy. francesco.fornai@med.unipi.it.

Abstract

The mammalian target of rapamycin (mTOR) is an ubiquitously expressed serine-threonine kinase, which senses and integrates several intracellular and environmental cues to orchestrate major processes such as cell growth and metabolism. Altered mTOR signalling is associated with brain malformation and neurological disorders. Emerging evidence indicates that even subtle defects in the mTOR pathway may produce severe effects, which are evident as neurological and psychiatric disorders. On the other hand, administration of mTOR inhibitors may be beneficial for a variety of neuropsychiatric alterations encompassing neurodegeneration, brain tumors, brain ischemia, epilepsy, autism, mood disorders, drugs of abuse, and schizophrenia. mTOR has been widely implicated in synaptic plasticity and autophagy activation. This review addresses the role of mTOR-dependent autophagy dysfunction in a variety of neuropsychiatric disorders, to focus mainly on psychiatric syndromes including schizophrenia and drug addiction. For instance, amphetamines-induced addiction fairly overlaps with some neuropsychiatric disorders including neurodegeneration and schizophrenia. For this reason, in the present review, a special emphasis is placed on the role of mTOR on methamphetamine-induced brain alterations.

KEYWORDS:

autophagy; mTOR; methamphetamine; protein aggregation; rapamycin; schizophrenia

PMID:
30061532
PMCID:
PMC6121884
DOI:
10.3390/ijms19082226
[Indexed for MEDLINE]
Free PMC Article

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