The mTOR pathway as a potential target for the development of therapies against neurological disease.
The mammalian target of rapamycin (mTOR) is a protein tyrosine kinase that regulates cell proliferation and survival via its effects on transcription, translation and autophagy. The activity of mTOR is controlled by a number of nutrient and energy sensing pathways, inhibiting cell proliferation under conditions of deprivation. In addition, mTOR has been associated with the inhibition of apoptosis and the clearance of toxic protein aggregates. Many neurodegenerative diseases are characterized by neuronal death via apoptosis, and it is possible that modulation of mTOR activity may offer some protection against their effects. In particular, diseases involving oxygen and nutrient deprivation, such as stroke, or diseases characterized by aggregate formation, such as Alzheimer's and Huntington's disease, could gain substantial benefit by either inhibiting or enhancing mTOR activity. In addition, inhibition of mTOR in cancerous tissue decreases cell proliferation and increases apoptosis, and is an effective therapy for brain tumors. In this article, the effects of mTOR and their potential usefulness for the treatment of neurological disease are examined.
Zemke
Daniel
D
Department of Neurology and Ophthalmology, Michigan State University, East Lansing, Michigan 48823, USA.
Azhar
Seema
S
Majid
Arshad
A
D000818:Animals; D006801:Humans; D008954:Models, Biological; D008958:Models, Molecular; D009422:Nervous System Diseases / Q000188:drug therapy* / Q000503:physiopathology; D011494:Protein Kinases / Q000737:chemistry / Q000502:physiology*; D017433:Protein Structure, Secondary; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D058570:TOR Serine-Threonine Kinases
D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases