Use of Resveratrol to treat experimental multiple sclerosis

University Of South Carolina At Columbia, Columbia SC

Investigators

Linked publications & trials

Abstract

Multiple Sclerosis (MS) is an autoimmune disease that affects ~400,000 people in the US. It is a life-long[unreadable] chronic disease diagnosed primarily in young adults. There is, as yet no cure for MS. The current treatment[unreadable] includes use of immunosuppressive drugs that often exhibit toxic side effects.Thus, there is a pressing need[unreadable] for alternate and more effective treatment strategies that target the components of inflammatory cells. CAM[unreadable] therapies constitute an important strategy to treat and control the disease. Experimental autoimmune[unreadable] encephalomyelitis is an animal model of MS induced by injection of self antigens, myelin basic protein,[unreadable] proteolipid protein or myelin oligodendrocyte glycoprotein and adjuvants. Resveratrol (RES; 3,5,4'-[unreadable] trihydroxystilbene), a nonflovaonoid polyphenol found in various plants including mulberries, peanuts and[unreadable] grapes has been shown to have beneficial effects particularly on cardiovascular diseases through its [unreadable] antiinflammatory properties. Our Preliminary Studies have demonstrated that RES induces apoptosis primarily [unreadable] in activated T cells through Fas-FasL interactions, involving aryl hydrocarbon receptor (AhR) and estrogen[unreadable] receptor (ER). Moreover, in vivo, RES down regulates CD44 and upregulates FoxpS. We are also excited by[unreadable] our findings that RES treatment decreases the inflammation and clinical symptoms of EAE. In the current[unreadable] study, we will test the central hypothesis that RES treatment is effective against EAE through multiple[unreadable] pathways incuding induction of apoptosis in myelin-specific T cells, suppression of DC functions, decreased[unreadable] T cell infiltration in the CMS due to CD44 down-regulation on T cells, and upregulation of T regs. We will[unreadable] pursue the specific aims: # 1. Study the role of Fas-FasL interactions in resveratrol (RES)-induced apoptosis[unreadable] in T cells and dendritic cells (DCs) involving autocrine or paracrine path ways.#2. Investigate the role of AhR[unreadable] in Fas-FasL upregulation and consequent apoptosis induced by RES in T cells.tf 3. Test the role of ER in the[unreadable] induction of apoptosis in T cells and peripheral T dysfunction following RES treatment.^ 4. Study the effect of[unreadable] RES on initiation and progression of EAE. These studies are aimed at providing insights into the efficacy of[unreadable] RES mainly in acute, remitting-relapsing and chronic forms of the disease which represent diverse[unreadable] pathological and immunological characteristics. Together, our studies should provide novel mechanistic[unreadable] clues on how RES helps in the treatment of MS and develop better CAM therapies to control the disease.[unreadable]