The Antioxidant Alpha-Lipoic Acid Studied For Possible Neuroprotective Properties

By VRP Staff

In a new study, researchers have found a possible explanation for the mechanism of action behind alpha-lipoic acid’s ability to protect neurons.

Neurodegenerative disorders include Alzheimer’s disease, dementia, Parkinson’s disease, and amyotrophic lateral sclerosis (Lou Gehrig’s disease, ALS). Neurodegeneration occurs when neurons in the brain and spinal cord fail to function. Because these cells do not easily regenerate en masse, excessive damage can occur in the brain.

Alpha-lipoic acid has recently been reported to afford protection against neurodegenerative disorders in humans and experimental animals. However, the mechanism by which lipoic acid accomplishes this neuroprotection has not been determined. Consequently, researchers in the current study decided to test lipoic acid’s effect on brain cells treated with peroxynitrite, a compound known to be involved in various neurodegenerative diseases. Researchers induced DNA strand breaks in the cells by stimulating the production of peroxynitrite.

When the cells were treated with lipoic acid, DNA strand breaks were significantly inhibited in a concentration-dependent manner. The lipoic acid appeared to stop the DNA breaks by reducing the generation of peroxynitrite.

In a second experiment, the lipoic acid also dramatically inhibited the DNA strand breaks when the DNA was treated directly with peroxynitrite.

Finally, in a third experiment, lipoic acid was able to stop the formation of hydroxyl radicals, harmful compounds that can damage nearly all types of macromolecules including carbohydrates, nucleic acids, lipids and amino acids.

“Taken together,” the researchers wrote, “these studies demonstrate for the first time that LA [lipoic acid] can potently inhibit peroxynitrite-mediated DNA strand breakage and hydroxyl radical formation. In view of the critical involvement of peroxynitrite in the pathogenesis of various neurodegenerative diseases, the inhibition of peroxynitrite-mediated DNA damage by LA may be responsible, at least partially, for its neuroprotective activities.”

Reference:

Jia Z, Zhu H, Vitto MJ, Misra BR, Li Y, Misra HP. Alpha-lipoic acid potently inhibits peroxynitrite-mediated DNA strand breakage and hydroxyl radical formation: implications for the neuroprotective effects of alpha-lipoic acid. Mol Cell Biochem. 2008 Dec 11. Published Online Ahead of Print.