Department Affiliation: Primary: Anesthesiology and Critical Care Medicine; Secondary: Pharmacology and Molecular Sciences
Degree: Ph.D., University of Montreal
Rank: Associate Professor
Telephone Number: 410-614-4859
Lab Number: 410-955-7272
Fax Number: 410-955-7271
E-mail address: sdore@jhmi.edu
School of Medicine Address: Ross 365 & Traylor 8th Floor, 720 Rutland Avenue, Baltimore, MD 21205
Battling Neurodegenerative Disorders: Stroke, Alzheimer and Aging
The goal of the team effort directed by Sylvain is to discover new effective 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 cute 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.
We also intend to understand of the protective role of the 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.
Our lab also provides molecular evidence for the potential therapeutic applications of complementary and alternative medicines. Using cultures of neurons, Sylvain 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 traditional medicine. Similar experiments and 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." 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.
Representative Publications:
Echeverria, V., Clerman, A. and Doré, S. (2005) Stimulation of PGE2 receptors EP2 and EP4 protects cultured neurons against oxidative stress and cell death following ß-amyloid exposure. Eur. J. Neurosci. 22:2199-2206, 2005. Pub Med Reference
- Doré, S. (2006) GPCR antagonists as an alternative to COX-2 inhibitors: a case for the PGE2 EP1 receptor. Trends Pharmacol. Sci. 27(9):458-460, 2006. Pub Med Reference
- Wang J, Doré S. Heme oxygenase-1 exacerbates early brain injury after intracerebral haemorrhage. Brain 130:1643-1652, 2007. Pub Med Reference
- Shah ZA, Li RC, Thimmulappa RK, Kensler TW, Yamamoto M, Biswal S, Doré S. Role of reactive oxygen species in modulation of Nrf2 following ischemic reperfusion injury. Neuroscience 147:53-59, 2007. Pub Med Reference
- Ahmad, A.S., Yun, Y.T., Ahmad, M., Maruyama, T., and Doré, S. (2008) Selective blockade of PGE2 EP1 receptor protects brain against experimental ischemia and excitotoxicity, and hippocampal slice cultures against oxygen-glucose deprivation. Neurotox. Research 14:343-351. Pub Med Reference
- Saleem, S., Zhuang, H., Biswal, S., Christen, Y., and Doré, S. (2008) Ginkgo biloba extract neuroprotective action is dependent on heme oxygenase 1 in ischemic reperfusion brain injury. Stroke 39:3389-3396. Pub Med Reference
- Li, R.C., Saleem, S., Zhen, G., Cao, W., Zhuang, H., Lee, J., Smith, A., Altruda, F., Tolosano, E., and Doré, S. Heme-hemopexin complex attenuates neuronal cell death and stroke damage. J. Cereb. Blood Flow & Metab. 29:953-964, 2009. Pub Med Reference
- Zeynalov, E., Shah, Z., Li, R., and Doré, S. Ischemic preconditioning induces protection against brain ischemia through heme oxygenase 1. Neurobiol. of Disease, 35:264-269, 2009. Pub Med Reference
- 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. Pub Med Reference
- Chaudhry, U.A., Zhuang, H., and Doré, S. Microsomal prostaglandin E synthase-2: Cellular distribution and expression in Alzheimer’s disease. Experimental Neurology, In Press, 2009. Pub Med Reference
Other graduate programs in which Dr. Dore participates:
