Researchers have hypothesized a mechanism for the known correlation between smoking and lowered risk for neurodegenerative diseases, and, if corroborated, the discovery may aid development of drugs with nicotine’s neuroprotective benefits, according to an article in the March issue of the Journal of Neurochemistry.

In the current work, American researchers demonstrated that nicotine inhibits activation of microglia, immune cells in the brain. Chronic microglial activation is a sign of the brain inflammation that is a key step in neuronal death. The researchers also identified the specific site, the alpha-7 acetylcholine receptor subtype, to which nicotine binds to block microglial activation.

“We propose that nicotine’s ability to prevent overactivation of microglia may be additional mechanism underlying nicotine’s neuroprotective properties in the brain,” said R. Douglas Shytle, PhD, lead author of the study.

“This finding lets us explore a new way of looking at neurodegenerative diseases like Alzheimer’s,” said Jun Tan, PhD, MD, principal investigator for the study. “A better understanding of the therapeutic aspects of nicotine may also help us develop drugs that mimic the beneficial action of nicotine without its unwanted side effects.”

Nicotine mimics the neurotransmitter acetylcholine, the major neurotransmitter lost in Alzheimer’s disease. The prevailing hypothesis among researchers is that nicotine helps protect the brain by binding to nicotinic acetylcholine receptors. The binding action causes brain cells to increase the release of neurotransmitters depleted in diseases like Alzheimer’s and Parkinson’s, offsetting the pathologic process.

The current study suggests that nicotine may also protect the brain through another, more indirect route -- by suppressing the hyperactivity of microglial cells that have targeted nearby neurons. In the normal, healthy brain microglia support and maintain neurons. They also help eliminate excess beta amyloid protein that accumulates in the brain with aging.

Based on their findings, the researchers hypothesize that acetylcholine acts as an endogenous anti-inflammatory substance to help prevent microglia from attacking the brain’s neurons. The neurotransmitter may consistently signal the brain’s immune system that everything is OK ? there is no need to activate more microglia. However, Shytle said, if the neurons that release acetylcholine begin to die and the acetylcholine signal fades, the microglia may become hyperactive and give rise to chronic inflammation that further aggravates neuronal loss.