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Neuroprotective, immunosuppressant and antineoplastic properties of mTOR inhibitors: current and emerging therapeutic options.

Abstract
The acronym mTOR defines a family of serine-threonine protein kinase called mammalian target of rapamycin. The major role of these kinases in the cell is to merge extracellular instructions with information about cellular metabolic resources and to control the rate of anabolic and catabolic processes accordingly. In mammalian cells mTOR is present in two distinct heteromeric protein complexes commonly referred to as mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2), involved in the control of a wide variety of cellular processes. It has been recently reported that compounds acting modulating mTOR activity, beside mediating the well recognized processes exploited in the anticancer and immunosuppressant effects, are provided with neuroprotective properties. In fact, mTOR is involved in the mechanism of PI3K/Akt-induced upregulation of glutamate transporter 1, GLT1, that is linked to several neuronal disorders such as stroke, Alzheimer's disease, and amyotrophic lateral sclerosis. Furthermore, in adult brain mTOR is crucial for numerous physiological processes such as synaptic plasticity, learning, memory, and brain control of food uptake. Moreover, the activation of mTOR pathway is involved in neuronal development, dendrite development and spine morphogenesis.
AuthorsGiuseppe Pignataro, Domenico Capone, Giuliano Polichetti, Antonio Vinciguerra, Antonio Gentile, Gianfranco Di Renzo, Lucio Annunziato
JournalCurrent opinion in pharmacology (Curr Opin Pharmacol) Vol. 11 Issue 4 Pg. 378-94 (Aug 2011) ISSN: 1471-4973 [Electronic] England
PMID21646048 (Publication Type: Journal Article, Review)
CopyrightCopyright © 2011 Elsevier Ltd. All rights reserved.
Chemical References
  • Antineoplastic Agents
  • Excitatory Amino Acid Transporter 2
  • Immunosuppressive Agents
  • Neuroprotective Agents
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
Topics
  • Animals
  • Antineoplastic Agents (pharmacology)
  • Excitatory Amino Acid Transporter 2 (metabolism)
  • Humans
  • Immunosuppressive Agents (pharmacology)
  • Neuroprotective Agents (pharmacology)
  • Phosphatidylinositol 3-Kinases (metabolism)
  • Proto-Oncogene Proteins c-akt (metabolism)
  • TOR Serine-Threonine Kinases (antagonists & inhibitors, metabolism)
  • Up-Regulation

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