β淀粉样蛋白与Alzheimer's病(4)
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关键词：β淀粉样蛋白,氧化应激,Alzheimer’s病 3. 展望 AD发病是包括基因，环境以及病理性致病因子在内的多种因素所导致的，针对不同的病因可能存在多种延缓此病进展的治疗方法。但对于Aβ神经毒性作用与神经退行性疾病特征性病理学、细胞结构与功能改变的关系研究无疑会有助于我们找到正确的神经保护措施。抗氧化治疗已经成为治疗AD的一个方面，褪黑素和维生素E已经开始应用于临床，并取得了一定的效果。鉴于Aβ借助金属离子的作用产生自由基的观点，金属离子螯合剂也开始被考虑用来治疗AD。另外，还可以通过拮抗Aβ发生毒性作用的受体如RAGE，或者利用钙离子通道拮抗剂来抑制Aβ的神经毒性。 总之，有关Aβ通过自由基升高来导致其神经毒性作用的研究结果已得到初步肯定，但其具体作用机制尚有待于进一步澄清，也将为AD的治疗提供更为广阔的前景。 参考文献 1.Vickers,J.C.Dickson,T.C.,Adlard,P.A.,Saunders,H.L.,King,C.E.,McCormack,G., The cause of neuronal degeneration in Alzheimer’s disease. Prog. Neurobiol. 2000;60:139-165. 2.Alzheimer disease ,2nd edition,edited by R.D.Terry,R.Katzman,K.L.Bick,and S.S.Sisodia.Lippincott Williams&Wilkins,Philadelphia copy 1999. 3.Hensley K,Hall N,Subramaniam R,Cole P,Harris M,Aksenova M,Aksenov M,Gabbita P,Carney J,Markesberry W,Butterfield DA.Brain regional correspondence between Alzheimer’s disease histopathology and biomarkers of protein oxidation.J Neurochem 1995;65:2146-56. 4.Bachurin S, Oxenkrug G, Lermontova N . N-acetylserotonin, melatonin and their derivatives improve cognition and protect against beta-amyloid-induced neurotoxicity. Ann N Y Acad Sci 1999;890:155-66 5.Subramaniam R,Koppal T,Yatin S,Jordan B,Butterfield DA.The free radical antioxidant vitamin E protects cortical synaptosomal membrane proteins from amyloid –peptide(25-35)toxicity but not from hydroxynonenal toxicity :relevance to the free radical hypothesis of Alzheimer’s disease.Neurochem Res 1998:23:1403-10. 6. Hensley K,Carney JM,Mattson MP,Aksenova M,Harris M,Wu JF,Floyd RA,Butterfield DA.A model for β-amyloid aggregation and neurotoxicity based free radical generation by the peptide:relevance to Alzheimer’s disease .Proc Natl Acad Sci USA 1994;91(8):3270-4 7. Harris M,Hensley K,Butterfield DA,Leedle RA,Carney JM.Direct evidence of oxidative injury produced by the Alzheimer’s βamyloid peptide (1-40)in cultured hippocampal neurons.Exp Neutol 1995;131:193-202 8. Servet M.Yatin,Sridhar Varadarajan,Christopher D.Allan Butterfield.In vitro and in vivo oxidative stress associated with Alzheimer’s amyloid β-peptide(1-42).Neurobiology of aging 1999;20:325-330. 9. Mark.R.J.,Lovell,M.A.,Markesbery,W.R.Uchida,K.,Mattson.M.P.A role for 4-hydroxynonenal ,an aldehydic product of lipid peroxidation,in disruption of ion homeostasis and neuronal death induced by amyloid β-peptide.J.Neurochem. 1997;68:255-264. 10. Gulyaeva, N. V. ; Victorov, I. V. ; Stepanichev, M. Y. ; Onufriev, M. V. Intracerebroventricular Administration of Beta-Amyloid Peptide (25-35) Induces Oxidative Stress and Neurodegeneration in Rat Brain. Advances in behavioral biology.1998; VOL 49 ：89-98. 11. Dikalov SI,Vitek MP,Maples KR,Mason RP.Amyloid βpeptides do not form peptide-derived free radicals spontaneously,but can enhance metal-catalyzed oxidation of hydroxylamines to nitroxides.J Biol Chem 1999;274(14):9392-99 12. Earl R.Stadtman,Rodney L.Levine.Oxidation of cellular proteins byβ-amyloid peptide.Neurobiology of aging 1999;20:331-333 13. Huang HM, Ou HC, Hsieh SJ, Chiang LY. Blockage of amyloid beta peptide-induced cytosolic free calcium by fullerenol-1, carboxylate C60 in PC12 cells. Life Sci 2000;66(16):1525-33. 14. Yan,S.D.,Chen,X.,Fu,J.,Chen.M.,Zhu,H.,Rother,A.,Slattery,RAGE and amyloid-beta peptide neurotoxicity in Alzheimer’s disease.Nature 382,685-691. 15. Dong W.Lee,Hyung O.Sohn,Heung B.Lim,et al .Alteration of free radical metabolism in the brain of mice infected with Scrapie agent.Free Rad.Res.,1999;30:499-507., 百拇医药