Use of Resveratrol to treat experimental multiple sclerosis

多发性硬化症(MS)是一种自身免疫性疾病，在美国约有40万人受到影响。这是一个终生的 主要在年轻人中诊断的慢性病。到目前为止，还没有治愈多发性硬化症的方法 包括使用经常表现出毒副作用的免疫抑制药物。因此，迫切需要 寻找针对炎症细胞成分的替代和更有效的治疗策略。凸轮 治疗是治疗和控制该病的重要策略。实验性自身免疫 脑脊髓炎是一种通过注射自身抗原、髓鞘碱性蛋白、 蛋白脂蛋白或髓鞘少突胶质细胞糖蛋白和佐剂。白藜芦醇(Res；3，5，4‘- 三羟基二苯乙烯)，是一种非花环类多酚，存在于各种植物中，包括桑树、花生和 葡萄已被证明具有有益的作用，特别是通过其对心血管疾病 抗炎性能。我们的初步研究表明，RES主要诱导细胞凋亡 通过Fas-FasL相互作用激活的T细胞，涉及芳烃受体(AhR)和雌激素 受体(ER)。此外，在体内，RES下调CD44，上调FoxpS。我们也对此感到兴奋 我们的研究发现，Res治疗可以减少EAE的炎症和临床症状。在当前 研究中，我们将检验Res治疗对EAE有效的中心假设 诱导髓鞘特异性T细胞凋亡、抑制DC功能的途径减少 CD_(44)下调T细胞表达，上调T_(Regs)表达，导致CMS中T细胞的浸润。我们会 追求特定目标：#1.研究Fas-FasL相互作用在白藜芦醇(Res)诱导的细胞凋亡中的作用 在T细胞和树突状细胞(DC)中，涉及自分泌或旁分泌途径。#2.研究AhR的作用 在RES诱导的T细胞Fas-FasL上调和随后的细胞凋亡中的作用。 Res治疗后T细胞凋亡和外周T细胞功能障碍的诱导。 对EAE的发生和发展的研究。这些研究的目的是为了解 Res主要表现为急性、缓解性复发和慢性形式的疾病，表现为多样化 病理和免疫学特征。总之，我们的研究应该提供新的机制 关于RES如何帮助治疗多发性硬化症并开发更好的CAM疗法来控制疾病的线索。

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