PMID- 33933601
OWN - NLM
STAT- MEDLINE
DCOM- 20210628
LR  - 20240402
IS  - 1873-4596 (Electronic)
IS  - 0891-5849 (Print)
IS  - 0891-5849 (Linking)
VI  - 169
DP  - 2021 Jun
TI  - mTOR in Alzheimer disease and its earlier stages: Links to oxidative damage in 
      the progression of this dementing disorder.
PG  - 382-396
LID - S0891-5849(21)00260-4 [pii]
LID - 10.1016/j.freeradbiomed.2021.04.025 [doi]
AB  - Alzheimer's disease (AD) is the most prevalent form of dementia in the elderly 
      population and has worldwide impact. The etiology of the disease is complex and 
      results from the confluence of multiple mechanisms ultimately leading to neuronal 
      loss and cognitive decline. Among risk factors, aging is the most relevant and 
      accounts for several pathogenic events that contribute to disease-specific toxic 
      mechanisms. Accumulating evidence linked the alterations of the mammalian target 
      of rapamycin (mTOR), a serine/threonine protein kinase playing a key role in the 
      regulation of protein synthesis and degradation, to age-dependent cognitive 
      decline and pathogenesis of AD. To date, growing studies demonstrated that 
      aberrant mTOR signaling in the brain affects several pathways involved in energy 
      metabolism, cell growth, mitochondrial function and proteostasis. Recent advances 
      associated alterations of the mTOR pathway with the increased oxidative stress. 
      Disruption of all these events strongly contribute to age-related cognitive 
      decline including AD. The current review discusses the main regulatory roles of 
      mTOR signaling network in the brain, focusing on its role in autophagy, oxidative 
      stress and energy metabolism. Collectively, experimental data suggest that 
      targeting mTOR in the CNS can be a valuable strategy to prevent/slow the 
      progression of AD.
CI  - Copyright (c) 2021 Elsevier Inc. All rights reserved.
FAU - Perluigi, M
AU  - Perluigi M
AD  - Department of Biochemical Sciences "A. Rossi-Fanelli", Sapienza University of 
      Rome, Piazzale A. Moro 5, 00185, Roma, Italy.
FAU - Di Domenico, F
AU  - Di Domenico F
AD  - Department of Biochemical Sciences "A. Rossi-Fanelli", Sapienza University of 
      Rome, Piazzale A. Moro 5, 00185, Roma, Italy.
FAU - Barone, E
AU  - Barone E
AD  - Department of Biochemical Sciences "A. Rossi-Fanelli", Sapienza University of 
      Rome, Piazzale A. Moro 5, 00185, Roma, Italy.
FAU - Butterfield, D A
AU  - Butterfield DA
AD  - Department of Chemistry, Sapienza University of Rome, Piazzale A. Moro 5, 00185, 
      Roma, Italy; Department of Chemistry and Sanders-Brown Center on Aging, 
      University of Kentucky, Lexington, KY, 40506-0055, USA. Electronic address: 
      dabcns@uky.edu.
LA  - eng
GR  - R01 AG060056/AG/NIA NIH HHS/United States
GR  - R56 AG055596/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Review
DEP - 20210430
PL  - United States
TA  - Free Radic Biol Med
JT  - Free radical biology & medicine
JID - 8709159
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Aged
MH  - *Alzheimer Disease
MH  - Autophagy
MH  - Humans
MH  - Oxidative Stress
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases/genetics/metabolism
PMC - PMC8145782
MID - NIHMS1701110
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - Oxidative stress
OT  - Protein aggregation
OT  - Proteostasis
OT  - mTOR
EDAT- 2021/05/03 06:00
MHDA- 2021/06/29 06:00
PMCR- 2022/06/01
CRDT- 2021/05/02 20:45
PHST- 2021/04/07 00:00 [received]
PHST- 2021/04/15 00:00 [accepted]
PHST- 2021/05/03 06:00 [pubmed]
PHST- 2021/06/29 06:00 [medline]
PHST- 2021/05/02 20:45 [entrez]
PHST- 2022/06/01 00:00 [pmc-release]
AID - S0891-5849(21)00260-4 [pii]
AID - 10.1016/j.freeradbiomed.2021.04.025 [doi]
PST - ppublish
SO  - Free Radic Biol Med. 2021 Jun;169:382-396. doi: 
      10.1016/j.freeradbiomed.2021.04.025. Epub 2021 Apr 30.