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Type-2 alkenes mediate synaptotoxicity in neurodegenerative diseases
Richard M Lopachin1, Terrence Gavin, David S Barber
1Department of Anesthesiology, Albert Einstein College of Medicine, Montefiore Medical Center, Moses Research Tower 7, 111 East 2210th Street, Bronx, NY 10467-2490, United States. lopachin@aecom.yu.edu
Neurotoxicology
|June 28, 2008
Summary
Oxidative stress in neurodegenerative diseases generates toxic compounds like acrolein and 4-hydroxy-2-nonenal (HNE), causing nerve damage. Environmental exposure to similar chemicals may accelerate disease progression.
Area of Science:
- Neuroscience
- Toxicology
- Biochemistry
Background:
- Synaptic dysfunction is an early hallmark of Alzheimer's, Parkinson's, and ALS.
- A common pathway involving oxidative stress, lipid peroxidation, and alpha,beta-unsaturated carbonyls (acrolein, HNE) is implicated.
Purpose of the Study:
- To review evidence linking endogenous acrolein and HNE to neurodegenerative synaptotoxicity.
- To propose a common mechanism of nerve terminal damage mediated by these compounds.
- To explore the role of environmental type-2 alkenes in accelerating neuropathogenesis.
Main Methods:
- Review of in vivo and in vitro studies on neurodegenerative diseases.
- Analysis of biochemical pathways involving oxidative stress and lipid peroxidation.
- Examination of the toxicological effects of alpha,beta-unsaturated carbonyls on neurons.
Main Results:
- Endogenous acrolein and HNE formation correlates with neuronal oxidative stress.
- These compounds form adducts with presynaptic proteins, leading to nerve terminal damage.
- Environmental type-2 alkenes share similar mechanisms of synaptotoxicity.
Conclusions:
- Endogenous acrolein and HNE are key mediators of regional synaptotoxicity in early neurodegenerative diseases.
- A common mechanism of nerve terminal damage is proposed for these conditions.
- Environmental exposure to type-2 alkenes may exacerbate neurodegeneration.
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