PMID- 29254095
OWN - NLM
STAT- MEDLINE
DCOM- 20190520
LR  - 20190520
IS  - 1875-8908 (Electronic)
IS  - 1387-2877 (Print)
IS  - 1387-2877 (Linking)
VI  - 62
IP  - 3
DP  - 2018
TI  - Dissecting the Role of 5-Lipoxygenase in the Homocysteine-Induced Alzheimer's 
      Disease Pathology.
PG  - 1337-1344
LID - 10.3233/JAD-170700 [doi]
AB  - Alzheimer's disease (AD) affects over 40 million patients around the world and 
      poses a huge economic burden on society since no effective therapy is available 
      yet. While the cause(s) for the most common sporadic form of the disease are 
      still obscure, lifestyle and different environmental factors have emerged as 
      modulators of AD susceptibility. Hyperhomocysteinemia (HHCY), a condition of high 
      circulating levels of homocysteine, is an independent but modifiable risk factor 
      for AD. Studies in AD mouse models have linked HHCY with memory impairment, 
      amyloidosis, tau pathology, synaptic dysfunction, and neuroinflammation. However, 
      the exact mechanism by which HHCY affects AD pathogenesis is unclear. The 
      5-lipoxygenase (5LO) is a protein upregulated in postmortem AD brains and plays a 
      functional role in AD pathogenesis. Recently, in vitro and in vivo studies showed 
      that HHCY effects on amyloid-beta and tau pathology, synapse and memory impairments 
      are dependent on the activation of the 5LO enzymatic pathway, since its genetic 
      absence or pharmacological inhibition prevents them. HHCY induces 5LO gene 
      upregulation by lowering the methylation of its promoter, which results in 
      increased translation and transcription of its mRNA. Based on these findings, we 
      propose that epigenetic modification of 5LO represents the missing biological 
      link between HHCY and AD pathogenesis, and for this reason it represents a viable 
      therapeutic target to prevent AD development in individuals bearing this risk 
      factor.
FAU - Di Meco, Antonio
AU  - Di Meco A
AD  - Alzheimer's Center at Temple, Lewis Katz School of Medicine Temple University, 
      Philadelphia, PA, USA.
FAU - Li, Jian-Guo
AU  - Li JG
AD  - Alzheimer's Center at Temple, Lewis Katz School of Medicine Temple University, 
      Philadelphia, PA, USA.
FAU - Pratico, Domenico
AU  - Pratico D
AD  - Alzheimer's Center at Temple, Lewis Katz School of Medicine Temple University, 
      Philadelphia, PA, USA.
LA  - eng
GR  - R01 HL112966/HL/NHLBI NIH HHS/United States
GR  - RF1 AG051684/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Review
PL  - Netherlands
TA  - J Alzheimers Dis
JT  - Journal of Alzheimer's disease : JAD
JID - 9814863
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - EC 1.13.11.34 (Arachidonate 5-Lipoxygenase)
SB  - IM
MH  - Alzheimer Disease/*enzymology/genetics/pathology
MH  - Animals
MH  - Arachidonate 5-Lipoxygenase/genetics/*metabolism
MH  - Brain/*enzymology
MH  - Epigenesis, Genetic
MH  - Homocysteine/metabolism
MH  - Humans
MH  - Hyperhomocysteinemia/*enzymology/genetics/pathology
PMC - PMC5869997
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - amyloid-beta
OT  - five-lipoxygenase
OT  - homocysteine
OT  - synapse
OT  - tau protein
EDAT- 2017/12/20 06:00
MHDA- 2019/05/21 06:00
PMCR- 2018/03/27
CRDT- 2017/12/20 06:00
PHST- 2017/12/20 06:00 [pubmed]
PHST- 2019/05/21 06:00 [medline]
PHST- 2017/12/20 06:00 [entrez]
PHST- 2018/03/27 00:00 [pmc-release]
AID - JAD170700 [pii]
AID - 10.3233/JAD-170700 [doi]
PST - ppublish
SO  - J Alzheimers Dis. 2018;62(3):1337-1344. doi: 10.3233/JAD-170700.