Dr. Doré’s Lab

Battling Neurodegenerative Disorders: Stroke, Alzheimer’s and Aging

Sylvain Dore PhD

The goal of the laboratory of Dr. Sylvain Doré is to discover new mechanisms that limit neuronal dysfunction associated with stroke, Alzheimer disease (AD), aging, and other neurological disorders. The overall goal is to slow down the progression of the disease, and ultimately stop it. To do so, the aim is to limit cell death (apoptosis and necrosis) resulting from either acute and/or chronic neurodegenerative conditions, re-establish normal cerebral blood flow, limit inflammation, and restore regular cellular functions. Using a variety of in vitro and in vivo protocols, several new hypotheses and potential therapies are being investigated and developed.

One objective is focused on understanding of protective role of heme metabolites in the brain using cellular/molecular techniques and various models of stroke, Alzheimer disease, and aging. New knowledge is gained specifically, by investigating the action and the role of activity of the heme oxygenase enzyme and its unique bioactive metabolites, namely, carbon monoxide, iron, biliverdin, and bilirubin.

We also intend to understand the actions of prostaglandin (PG) metabolites, which are generated by the degradation of arachidonic acid by cyclooxygenase (COX) enzymes. COX is the rate-limiting enzyme for the production of PGs, which are key elements in the inflammatory response. The resulting consequences are suggested to play an important role in the loss of normal neuronal functions associated with aging and neurodegenerative disorders.

Thirdly our lab provides molecular evidence for the potential therapeutic applications of complementary and alternative medicines (CAM). Using cultures of neurons, Dr. Doré has observed that pre-treatment with a standardized extract of Ginkgo biloba could alter the presence of specific genes/proteins important in neuronal function. Individual components of the extract are ineffective, supporting the synergistic principals of Chinese medicine. Similar experiments and results have been obtained using resveratrol, which appears to be an active ingredient concentrated in red wines, and which has been proposed to explain some of the beneficial effects associated with the so called “French Paradox.” These alternative medicines could provide resistance against damage induced by free radicals, the toxins that are generated with aging and are the hallmark of many neurodegenerative processes. Ultimately, the aim is to perform basic research using innovative tools to test original hypotheses and find new treatments that could have clinical applications for the population.

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