PMID- 25105207
OWN - NLM
STAT- MEDLINE
DCOM- 20150713
LR  - 20220316
IS  - 1365-2060 (Electronic)
IS  - 0785-3890 (Print)
IS  - 0785-3890 (Linking)
VI  - 46
IP  - 8
DP  - 2014 Dec
TI  - Taking aim at Alzheimer's disease through the mammalian target of rapamycin.
PG  - 587-96
LID - 10.3109/07853890.2014.941921 [doi]
AB  - A significant portion of the world's population suffers from sporadic Alzheimer's 
      disease (AD) with available present therapies limited to symptomatic care that 
      does not alter disease progression. Over the next decade, advancing age of the 
      global population will dramatically increase the incidence of AD and severely 
      impact health care resources, necessitating novel, safe, and efficacious 
      strategies for AD. The mammalian target of rapamycin (mTOR) and its protein 
      complexes mTOR Complex 1 (mTORC1) and mTOR Complex 2 (mTORC2) offer exciting and 
      unique avenues of intervention for AD through the oversight of programmed cell 
      death pathways of apoptosis, autophagy, and necroptosis. mTOR modulates 
      multi-faceted signal transduction pathways that involve phosphoinositide 3-kinase 
      (PI 3-K), protein kinase B (Akt), hamartin (tuberous sclerosis 1)/ tuberin 
      (tuberous sclerosis 2) (TSC1/TSC2) complex, proline-rich Akt substrate 40 kDa 
      (PRAS40), and p70 ribosomal S6 kinase (p70S6K) and can interface with the 
      neuroprotective pathways of growth factors, sirtuins, wingless, forkhead 
      transcription factors, and glycogen synthase kinase-3beta. With the ability of mTOR 
      to broadly impact cellular function, clinical strategies for AD that implement 
      mTOR must achieve parallel objectives of protecting neuronal, vascular, and 
      immune cell survival in conjunction with preserving networks that determine 
      memory and cognitive function.
FAU - Maiese, Kenneth
AU  - Maiese K
AD  - Cellular and Molecular Signaling , Newark, New Jersey 07101 , USA.
LA  - eng
GR  - R01 NS053946/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20140808
PL  - England
TA  - Ann Med
JT  - Annals of medicine
JID - 8906388
RN  - 0 (Multiprotein Complexes)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 2)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Alzheimer Disease/*metabolism
MH  - Apoptosis
MH  - Humans
MH  - Mechanistic Target of Rapamycin Complex 1
MH  - Mechanistic Target of Rapamycin Complex 2
MH  - Memory/physiology
MH  - Multiprotein Complexes/metabolism
MH  - Oxidative Stress
MH  - *Signal Transduction
MH  - TOR Serine-Threonine Kinases/*metabolism
PMC - PMC4250432
MID - NIHMS620826
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - amyloid
OT  - apoptosis
OT  - autophagy
OT  - mTORC1
OT  - mTORC2
OT  - mammalian target of rapamycin (mTOR)
OT  - necroptosis
OT  - oxidative stress
OT  - rapamycin
COIS- Declaration of interest: The authors declare no conflicts of interest.
EDAT- 2014/08/12 06:00
MHDA- 2015/07/15 06:00
PMCR- 2015/12/01
CRDT- 2014/08/09 06:00
PHST- 2014/08/09 06:00 [entrez]
PHST- 2014/08/12 06:00 [pubmed]
PHST- 2015/07/15 06:00 [medline]
PHST- 2015/12/01 00:00 [pmc-release]
AID - 10.3109/07853890.2014.941921 [doi]
PST - ppublish
SO  - Ann Med. 2014 Dec;46(8):587-96. doi: 10.3109/07853890.2014.941921. Epub 2014 Aug 
      8.