张新燕;原铂尧;赵金;高晓红;孙静洁;王满侠;

• 1:兰州大学第二医院

摘要(Abstract)：

多发性硬化(multiple sclerosis,MS)是中枢神经系统(central nervous system,CNS)自身免疫性脱髓鞘疾病,是导致年轻人致残的最主要的CNS疾病,发病机制尚不明确。自噬(autophagy)是细胞降解和回收利用细胞内生物大分子与细胞器的过程,是细胞重要的自稳机制,已经发现其在神经退行性疾病细胞代谢中有重要作用,如阿尔兹海默病,同时,自噬也参与进自身免疫的调节,也许对于MS的疾病病理过程有重要作用。

关键词(KeyWords)： 多发性硬化;自噬;EBV;瓜氨酸化;中枢神经系统

Abstract:

Keywords:

基金项目(Foundation): 甘肃省国际科技合作专项(编号:1604WKCA015)

作者(Authors): 张新燕;原铂尧;赵金;高晓红;孙静洁;王满侠;

参考文献(References)：

• [1]Xie Z,Klionsky DJ.Autophagosome formation:core machinery and adaptations[J].Nat Cell Biol,2007,9(10):1102-1 209.
• [2]Ohsumi Y.Molecular dissection of autophagy:two ubiquitin-like systems[J].Nat Rev Mol Cell Biol,2001,2(3):211-216.
• [3]Suzuki K,Ohsumi Y.Molecular machinery of autophagosome formation in yeast,Saccharomyces cerevisiae[J].FEBS Lett,2007,581(11):2 156-2 161.
• [4]Cecconi F,Levine B.The role of autophagy in mammalian development:cell makeover rather than cell death[J].Dev Cell,2008,15(3):344-357.
• [5]Burman C,Ktistakis NT.Autophagosome formation in mammalian cells.Semin Immunopathol[J].2010,32(4):397-413.
• [6]Keller CW,Lünemann JD.Autophagy and AutophagyRelated Proteins in CNS Autoimmunity[J].Front Immunol,2017,8:165.
• [7]Feng Y,He D,Yao Z.The machinery of macroautophagy[J].Cell Res,2014,24(1):24-41.
• [8]Pua HH,Dzhagalov I,Chuck M.A critical role for the autophagy gene Atg5in T cell survival and proliferation[J].J Exp Med,2007,204(1):25-31.
• [9]Kovacs JR,Li C,Yang Q.Autophagy promotes T-cell survival through degradation of proteins of the cell death machinery[J].Cell Death Differ,2012,19(1):144-152.
• [10]Alirezaei M,Fox HS.Elevated ATG5expression in autoimmune demyelination and multiple sclerosis[J].Autophagy,2009,5(2):152-158.
• [11]Miller BC,Zhao Z,Stephenson LM,et al.The autophagy gene ATG5 plays an essential role in B lymphocyte development[J].Autophagy,2008,4(3):309-314.
• [12]Nimmerjahn F,Milosevic S.Major histocompatibility complex class II-restricted presentation of a cytosolic antigen by autophagy[J].Eur J Immunol,2003,33(5):1 250-1 259.
• [13]Stys PK,Zamponi GW.Will the real multiple sclerosis please stand up[J].Nat Rev Neurosci,2012,13(7):507-514.
• [14]Savina A,Jancic C.NOX2controls phagosomal pH to regulate antigen processing during crosspresentation by dendritic cells[J].Cell,2006,126(1):205-218.
• [15]Fader CM,Colombo MI.Autophagy and multivesicular bodies:two closely related partners[J].Cell Death Differ,2009,16(1):70-78.
• [16]Münz C.Enhancing immunity through autophagy[J].Annu Rev Immunol,2009,27:423-449.
• [17]Nguyen H,James EA.Immune recognition of citrullinated epitopes[J].Immunology,2016,149(2):131-138.
• [18]Blum JS,Wearsch PA,Cresswell P.Pathways of antigen processing[J].Annu Rev Immunol,2013,31:443-473.
• [19]BirgisdottirB,Lamark T,Johansen T.The LIR motifcrucial for selective autophagy[J].J Cell Sci,2013,126(Pt 15):3 237-3 247.
• [20]'tHart BA,Kap YS,Morandi E.EBV Infection and Multiple Sclerosis:Lessons from a Marmoset Model[J].Trends Mol Med,2016,22(12):1 012-1 024.
• [21]Hartford CM,Ratain MJ.Rapamycin:something old,something new,sometimes borrowed and now renewed[J].Clin Pharmacol Ther,2007,82(4):381-388.
• [22]Esposito M,Ruffini F.Rapamycin inhibits relaps-ing experimental autoimmune encephalomyelitis by both effector and regulatory T cells modulation[J].J Neuroimmunol,2010,220(1/2):52-63.
• [23]Li Z,Chen L,Niu X,et al.Immunomodulatory synergy by combining atorvastatin and rapamycin in the treatment of experimental autoimmune encephalomyelitis(EAE)[J].J Neuroimmunol,2012,250(1/2):9-17.
• [24]Lisi L,Navarra P,Cirocchi R,et al.Rapamycin reduces clinical signs and neuropathic pain in a chronic model of experimental autoimmune encephalomyelitis[J].J Neuroimmunol,2012,243(1/2):43-51.
• [25]Dello RC,Lisi L,Feinstein DL.mTOR kinase,a key player in the regulation of glial functions:relevance for the therapy of multiple sclerosis[J].Glia,2013,61(3):301-311.