PMID- 26569216
OWN - NLM
STAT- MEDLINE
DCOM- 20160819
LR  - 20200225
IS  - 1420-3049 (Electronic)
IS  - 1420-3049 (Linking)
VI  - 20
IP  - 11
DP  - 2015 Nov 12
TI  - alpha-Linolenic Acid, A Nutraceutical with Pleiotropic Properties That Targets 
      Endogenous Neuroprotective Pathways to Protect against Organophosphate Nerve 
      Agent-Induced Neuropathology.
PG  - 20355-80
LID - 10.3390/molecules201119698 [doi]
AB  - alpha-Linolenic acid (ALA) is a nutraceutical found in vegetable products such as 
      flax and walnuts. The pleiotropic properties of ALA target endogenous 
      neuroprotective and neurorestorative pathways in brain and involve the 
      transcription factor nuclear factor kappa B (NF-kappaB), brain-derived neurotrophic 
      factor (BDNF), a major neuroprotective protein in brain, and downstream signaling 
      pathways likely mediated via activation of TrkB, the cognate receptor of BDNF. In 
      this review, we discuss possible mechanisms of ALA efficacy against the highly 
      toxic OP nerve agent soman. Organophosphate (OP) nerve agents are highly toxic 
      chemical warfare agents and a threat to military and civilian populations. Once 
      considered only for battlefield use, these agents are now used by terrorists to 
      inflict mass casualties. OP nerve agents inhibit the critical enzyme 
      acetylcholinesterase (AChE) that rapidly leads to a cholinergic crisis involving 
      multiple organs. Status epilepticus results from the excessive accumulation of 
      synaptic acetylcholine which in turn leads to the overactivation of muscarinic 
      receptors; prolonged seizures cause the neuropathology and long-term consequences 
      in survivors. Current countermeasures mitigate symptoms and signs as well as 
      reduce brain damage, but must be given within minutes after exposure to OP nerve 
      agents supporting interest in newer and more effective therapies. The pleiotropic 
      properties of ALA result in a coordinated molecular and cellular program to 
      restore neuronal networks and improve cognitive function in soman-exposed 
      animals. Collectively, ALA should be brought to the clinic to treat the long-term 
      consequences of nerve agents in survivors. ALA may be an effective therapy for 
      other acute and chronic neurodegenerative disorders.
FAU - Piermartiri, Tetsade
AU  - Piermartiri T
AD  - Molecular and Cellular Biology Graduate School Program, Uniformed Services 
      University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, 
      USA. tetsade@yahoo.com.br.
FAU - Pan, Hongna
AU  - Pan H
AD  - Department of Neurology and Program in Neuroscience, Uniformed Services 
      University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, 
      USA. hongna.pan@usuhs.edu.
FAU - Figueiredo, Taiza H
AU  - Figueiredo TH
AD  - Department of Anatomy, Physiology and Genetics, Uniformed Services University of 
      the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA. 
      taiza.figueiredo.ctr@usuhs.edu.
FAU - Marini, Ann M
AU  - Marini AM
AD  - Department of Neurology and Program in Neuroscience, Uniformed Services 
      University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, 
      USA. ann.marini@usuhs.edu.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20151112
PL  - Switzerland
TA  - Molecules
JT  - Molecules (Basel, Switzerland)
JID - 100964009
RN  - 0 (Antidepressive Agents)
RN  - 0 (Nerve Agents)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Organophosphates)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 0RBV727H71 (alpha-Linolenic Acid)
SB  - IM
MH  - Animals
MH  - Antidepressive Agents/pharmacology/therapeutic use
MH  - Brain/drug effects/metabolism
MH  - Cognition/drug effects
MH  - Cognition Disorders/drug therapy/etiology/metabolism
MH  - *Dietary Supplements
MH  - Humans
MH  - Models, Animal
MH  - Nerve Agents/*adverse effects
MH  - Nervous System Diseases/chemically induced/drug therapy/metabolism
MH  - Neurodegenerative Diseases/drug therapy/etiology/metabolism
MH  - Neuropathology
MH  - Neuroprotection/*drug effects
MH  - Neuroprotective Agents/*pharmacology/therapeutic use
MH  - Organophosphates/*adverse effects
MH  - Receptors, N-Methyl-D-Aspartate/metabolism
MH  - Signal Transduction/*drug effects
MH  - alpha-Linolenic Acid/*pharmacology/therapeutic use
PMC - PMC6332275
OTO - NOTNLM
OT  - BDNF
OT  - mTOR
OT  - natural product
OT  - neuroprotection
OT  - neurorestoration
OT  - nutraceutical
OT  - pleiotropic
OT  - rat
OT  - soman
OT  - alpha-linolenic acid
COIS- The views of the authors do not reflect any position or policies of the U.S. Army 
      or the Department of Defense.
EDAT- 2015/11/17 06:00
MHDA- 2016/08/20 06:00
PMCR- 2015/11/12
CRDT- 2015/11/17 06:00
PHST- 2015/10/08 00:00 [received]
PHST- 2015/10/29 00:00 [revised]
PHST- 2015/11/03 00:00 [accepted]
PHST- 2015/11/17 06:00 [entrez]
PHST- 2015/11/17 06:00 [pubmed]
PHST- 2016/08/20 06:00 [medline]
PHST- 2015/11/12 00:00 [pmc-release]
AID - molecules201119698 [pii]
AID - molecules-20-19698 [pii]
AID - 10.3390/molecules201119698 [doi]
PST - epublish
SO  - Molecules. 2015 Nov 12;20(11):20355-80. doi: 10.3390/molecules201119698.