Alzheimer’s Research Grants Awarded to VCU Faculty

By Malorie Burkett

Four Virginia Commonwealth University professors have been awarded grants through the 2011-2012 Alzheimer’s and Related Diseases Research Award Fund (ARDRAF).

Malgorzata Dukat, Ph.D., associate professor in the Department of Medicinal Chemistry, and Galia R. Abdrakhmanova, M.D., Ph.D., assistant professor in the Department of Pharmacology and Toxicology, are researching small molecules as negative allosteric modulators of 7 nAChRs.

Evidence suggests that aspects of Alzheimer's disease are related to an imbalance of the substance acetylcholine (ACh) – a neurotransmitter found in the brain as well as in other parts of the body that produces its effects by acting on cholinergic receptors, or specialized sensory nerve endings that respond to the stimulation of ACh.

Proper functioning of the cholinergic system is critical for an individual’s well-being and normal operation of the nervous system. These effects are mediated by different types of cholinergic receptors that have the common ability to respond to ACh.  A goal is to preferentially target one of these ACh receptor subtypes over the others.

The researchers have identified MD-354 as a negative allosteric modulator of a particular subtype of cholinergic receptors – in other words, the 7 receptors, that has been implicated in Alzheimer's disease. This agent could be of value in treating the disease because it selectively targets 7 allosteric sites. A goal of their work is to optimize the actions of this agent by using techniques to design and synthesize the appropriate analogs. The new analogs of MD-354 will be examined for their ability to selectively function at 7 cholinergic receptors using electrophysiological methods.

Aron H. Lichtman, Ph.D., and Laura E. Wise, Ph.D., professors in the Department of Pharmacology and Toxicology, are targeting the endogenous cannabinoid system to treat Alzheimer’s disease.

Cannabinoids have been demonstrated to inhibit or reduce the deposition of beta-amyloid plaques—deposits found in the brain of Alzheimer's disease patients. Drugs that elevate naturally occurring cannabinoids without producing psychomimetic effects and cognitive impairing actions are particularly attractive therapeutic targets.

This study will evaluate whether a drug that prevents degradation of endocannabinoids – chemical substances in the body resembling organic chemicals found in cannabis – will prevent the development of learning and memory deficits, as well as the neuropathological markers of AD in a well-established animal model.

The ARDRAF was established by the Virginia General Assembly in 1982 to stimulate innovative investigations into Alzheimer's disease and related disorders along a variety of avenues, such as the causes, epidemiology, diagnosis and treatment of the disorder; public policy and the financing of care; and the social and psychological impacts of the disease upon the individual, family and community.

The ARDRAF competition is administered by VCU’s Virginia Center on Aging. In addition, researchers from George Mason University also have been awarded ARDRAF grants this year. 

For more information, visit http://www.sahp.vcu.edu/vcoa/.