Battling Neurodegenerative Disorders: Stroke, Alzheimer’s and Aging
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 the 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.
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.
Sylvain Doré, PhD, FAHA
Professor of Anesthesiology, Neurology, Psychiatry, Psychology, Pharmaceutics and Neuroscience;
Director of Research Programs, Department of Anesthesiology;
Investigator, Center for Translational Research in Neurodegenerative Disease (CTRND)
Investigator, McKnight Brain Institute (MBI)
Post Doc, Neuroscience (Sol Snyder), Johns Hopkins University, 1999
Post Doc, Psychiatry (Remi Quirion), McGill University, 1996
PhD, Biomedical Sciences, University of Montreal, 1994
MS, Pharmacology, University of Quebec, 1990
BS, Biochemistry, University of Quebec, 1988
Contact Dr. Doré
- Leonardo CC, Mendes M, Ahmad AS, Doré S. Efficacy of prophylactic flavan-3-ol in permanent focal ischemia in twelve-month-old mice. Am. J Physiol. Hearty Circ Physiol 308:H583-91, 2015.
- Leclerc JL, Blackburn S, Neal D, Mendez NV, Wharton JA, Waters MF, Doré S. Haptoglobin phenotype predicts the development of focal and global cerebral vasospasm and may influence outcomes after aneurysmal subarachnoid hemorrhage. Proc Natl Acad Sci USA 112:1155-60, 2015.
- Leclerc JL, Lampert AS, Diller, MA, Doré S. Genetic deletion of the PGE2 EP3 receptor improves anatomical and functional outcomes after intracerebral hemorrhage. Eur. J Neuroscience 41:1301-91, 2015.
- Glushakov AV, Fazal J, Doré S. Role of the prostaglandin E2 EP1 receptor in traumatic brain injury. PLOS One9(11):e113689, 2014.
- Bickford JS, Ali NF, Nick JA, Al-Yahia M, Beachy DE, Doré S, Nick H, Waters M. Endothelin-1-mediated vasoconstriction alters cerebral gene expression in iron homeostasis and eicosanoid metabolism. Brain Res., 1588:25–36, 2014.
- Hawkins KE, DeMars KM, Singh J, Yang C, Cho HS, Frankowski JC, Doré S, Candelario-Jalil E. Neurovascular protection by post-ischemic intravenous injections of the lipoxin A4 receptor agonist, BML-111, in a rat model of ischemic stroke. J. Neurochemistry 129:130-42, 2014.
- Ahmad AS, Maruyama T, Narumiya S, Doré S. PGE2 EP1 Receptor Deletion Attenuates 6-OHDA-Induced Parkinsonism in Mice: Old Switch, New Target. Neurotox Res. 23:260-6. 2013.
- Leonardo CC, Agrawal M, Singh N, Moore JR, Biswal S, Doré S, Oral administration of the flavanol (–)-epicatechin bolsters endogenous protection against focal ischemia through the Nrf2 cytoprotective pathway. Eur. J. Neuroscience 38:3659-68, Dec 2013. PMID: 24112193