Dr. Sylvain Doré
Battling Neurodegenerative Disorders: Stroke, Alzheimer’s and Aging
Professor of Anesthesiology, Neurology, Psychiatry, Psychology, Pharmaceutics,and Neuroscience;
Director of Research Programs, Department of Anesthesiology;
Investigator, McKnight Brain Institute and CTRND
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
Research Focus and Aims
The goal of the team effort directed by Sylvain is to discover new effective mechanisms that limit neuronal dysfunction associated with ischemic and hemorrhagic Stroke, Alzheimer disease (AD), Aging, and various 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 neuron death (apoptosis and necrosis) resulting from 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 preclinical models, several new hypotheses and potential therapies are being investigated and developed:
- One objective is focused on understanding the actions of prostaglandin (PG) metabolites generated by the degradation of arachidonic acid by cyclooxygenase enzymes. These enzymes are the rate-limiting steps 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. This work is supported in part by NIH/NINDS
- We also intend to understand of the protective role of the heme metabolites in the brain using cellular/molecular techniques and various models of ischemic and hemorrhagic stroke, AD, 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.
- Our lab also provides molecular evidence for the potential therapeutic applications of complementary and alternative medicines. Using cultures of neurons it was observed that treatment with a standardized extracts of Korean Ginseng or of Ginkgo biloba could alter the presence of specific genes/proteins important in neuronal function. The lab is exploring the regulation of the transcriptional factor Nrf2, and the increased expression of phase 2 protective enzymes, notably heme oxygenase. Also results have been obtained using resveratrol and other polyphenols, which appear to be active ingredients concentrated in red wines, and which has been proposed to explain some of the beneficial effects associated with the so called “French Paradox.” Similarly, experiments have provided evidence for a unique protective mechanism for the flavanol epicatechin which can be enriched in dark chocolate. These bioactive nutrients could provide resistance against damage induced by free radicals, the toxins which are generated with aging and are the hallmark of many neurodegenerative processes. This work is supported in part by NIH/NCCAM
Join the team!
Volunteers are now being accepted for conducting research in Dr. Sylvain Doré’s lab. The team focuses on investigating novel treatments of neurological disorders. Specifically, current projects involve the utilization of various preclinical mouse models to uncover the neurobiological processes of ischemic and hemorrhagic strokes, and those associated with Aging, Alzheimer disease and other related vascular cognitive impairments. The lab is especially interested in inflammation, antioxidants and natural products. Volunteers will have the opportunity to learn about the rigorous process of scientific inquiry and gain hands-on experience conducting experiments (for example, PCR-genotyping, perfusion, brain harvesting, slicing, staining, and quantification/analysis, etc). Those interested will be asked to commit an average of 3 X 4h-block/week; additionally, summer “internship” is encouraged. Please email us if you are interested in volunteering or would like more information about this exciting opportunity
- Doré, S. GPCR antagonists as an alternative to COX-2 inhibitors: a case for the PGE2 EP1 receptor. Trends Pharmacol Sci 27:458-60, 2006.
- Li Rc, Saleem S, Zhen G, Cao W, Zhuang H, Lee J, Smith A, Altruda F, Tolosano E, Doré S. Heme-hemopexin complex attenuates neuronal cell death and stroke damage. J Cerebr Blood Flow & Metab, 29:953-64, 2009.
- Sen, N., Hara, M.R., Ahmad, A.S., Cascio, M.B., Kamiya, A., Ehmsen, J.T., Aggrawal, N., Hester, L., Doré, S., Snyder, S.H., and Sawa, A. GOSPEL: A novel neuroprotective protein that binds to GAPDH upon S-nitrosylation. Neuron 63:81-91, 2009.
- Chaudhry UA, Zhuang H, Doré S. Microsomal prostaglandin E synthase-2: Cellular distribution and expression in Alzheimer’s disease. Exp. Neurology. 223:359-65, 2010.
- Mustafa AK, Zeynalov E, Ahmad AS, Gazi SK, Sikka G, Ehmsen JT, Barrow RK, Coyle JT, Snyder SH, Doré S. Serine racemase deletion protects against ischemic injury. J. Neurosci. 30:1413-6, 2010.
- Sakata Y, Zhuang H, Kwansa H, Koehler, RC, Doré S. Resveratrol protects against experimental stroke: Putative neuroprotective role of heme oxygenase 1. Exp. Neurology 224:325-9, 2010.
- Shah ZA, Li R, Ahmad AS, Kensler TW, Yamamoto M, Biswal S, Doré S. The flavanol (–)-epicatechin prevents stroke damage through the Nrf2-HO1 pathway. J. Cerebr. Blood Flow & Metab. 30:1951-61, 2010.
- Wang B, Cao W, Biswal, S, Doré S. Carbon monoxide-activated Nrf2 pathway leads to protection against permanent focal cerebral ischemia. Stroke, 42:2605-10, 2011.
- Mohan S, Ahmad AS, Glushakov AV, Chambers C, Doré S. Putative role of prostaglandin receptor in intracerebral hemorrhage. Front Neurol. 3:145, 2012.
- Wang B, Zhu X, Kim YT, Li J, Huang S, Saleem S, Li RC, Xuc Y, Doré S, Cao W. Histone deacetylase inhibition activates transcription factor Nrf2 and protects against cerebral ischemic damage. Free Radical Biol. & Med., 52:928-36, 2012.
- Zhen G, Kim YT, Li RC, Yocum J, Kapoor N, Langer J, Dobrowolski P, Maruyama S, Narumiya S, Doré S. PGE2 EP1 receptor exacerbated neurotoxicity in mouse cerebral ischemia and Alzheimer’s disease. Neurobiology of Aging, Epub 18 October 2011.
- Kim YT, Moon SK, Maruyama T, Narumiya S, Doré S. Prostaglandin FP receptor inhibitor reduces ischemic brain damage and neurotoxicity. Neurobiol Dis. 48:58-65, 2012.
- 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. 2013 Feb 6. [Epub ahead of print] PMID: 23385625