PMID- 25796566
OWN - NLM
STAT- MEDLINE
DCOM- 20160926
LR  - 20220409
IS  - 1095-953X (Electronic)
IS  - 0969-9961 (Linking)
VI  - 84
DP  - 2015 Dec
TI  - mTOR signaling in aging and neurodegeneration: At the crossroad between 
      metabolism dysfunction and impairment of autophagy.
PG  - 39-49
LID - S0969-9961(15)00086-8 [pii]
LID - 10.1016/j.nbd.2015.03.014 [doi]
AB  - Compelling evidence indicates that the mammalian target of rapamycin (mTOR) 
      signaling pathway is involved in cellular senescence, organismal aging and 
      age-dependent diseases. mTOR is a conserved serine/threonine kinase that is known 
      to be part of two different protein complexes: mTORC1 and mTORC2, which differ in 
      some components and in upstream and downstream signalling. In multicellular 
      organisms, mTOR regulates cell growth and metabolism in response to nutrients, 
      growth factors and cellular energy conditions. Growing studies highlight that 
      disturbance in mTOR signalling in the brain affects multiple pathways including 
      glucose metabolism, energy production, mitochondrial function, cell growth and 
      autophagy. All these events are key players in age-related cognitive decline such 
      as development of Alzheimer disease (AD). The current review discusses the main 
      regulatory roles of mTOR signalling in the brain, in particular focusing on 
      autophagy, glucose metabolism and mitochondrial functions. Targeting mTOR in the 
      CNS can offer new prospective for drug discovery; however further studies are 
      needed for a comprehensive understanding of mTOR, which lies at the crossroads of 
      multiple signals involved in AD etiology and pathogenesis.
CI  - Copyright (c) 2015 Elsevier Inc. All rights reserved.
FAU - Perluigi, Marzia
AU  - Perluigi M
AD  - Department of Biochemical Sciences, Sapienza University of Rome, Italy. 
      Electronic address: Marzia.perluigi@uniroma1.it.
FAU - Di Domenico, Fabio
AU  - Di Domenico F
AD  - Department of Biochemical Sciences, Sapienza University of Rome, Italy.
FAU - Butterfield, D Allan
AU  - Butterfield DA
AD  - Sanders-Brown Centre of Aging, University of Kentucky, Lexington KY, USA; 
      Department of Chemistry, University of Kentucky, Lexington KY, USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20150319
PL  - United States
TA  - Neurobiol Dis
JT  - Neurobiology of disease
JID - 9500169
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Aging/*metabolism
MH  - Animals
MH  - Autophagy/*physiology
MH  - Brain/metabolism
MH  - Humans
MH  - Neurodegenerative Diseases/drug therapy/*metabolism
MH  - TOR Serine-Threonine Kinases/*metabolism
OTO - NOTNLM
OT  - Alzheimer disease
OT  - Autophagy
OT  - Down Syndrome
OT  - mTOR
EDAT- 2015/03/23 06:00
MHDA- 2016/09/27 06:00
CRDT- 2015/03/23 06:00
PHST- 2015/01/29 00:00 [received]
PHST- 2015/03/09 00:00 [revised]
PHST- 2015/03/12 00:00 [accepted]
PHST- 2015/03/23 06:00 [entrez]
PHST- 2015/03/23 06:00 [pubmed]
PHST- 2016/09/27 06:00 [medline]
AID - S0969-9961(15)00086-8 [pii]
AID - 10.1016/j.nbd.2015.03.014 [doi]
PST - ppublish
SO  - Neurobiol Dis. 2015 Dec;84:39-49. doi: 10.1016/j.nbd.2015.03.014. Epub 2015 Mar 
      19.