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雷帕霉素抗神经退行性病研究进展 被引量：2

Review on Rapamycin as a potential therapeutic agent against neurodegenerative disease
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摘要 雷帕霉素作为一种传统的抗真菌药物,具有免疫抑制剂和抗肿瘤的作用。值得注意的是,它通过抑制哺乳动物雷帕霉素靶标蛋白mTOR、受体FKBP、VMP1,促进自噬,抑制了帕金森病、亨廷顿病等神经退行性变的病理过程,从而有望成为一种新的抗神经退行病药物。本文对其新的研究进展予以综述。 Autophagy contributes to the pathology of various neurodegenerative conditions. gainst Candida albicans or immunosuppressive, was found to be effective against tumor. duces autophagy by inactivating the protein mammalian target of rapamycin （ roTOR）, could offer a tractable therapeutic agent for neurodegenerative diseases. Rapamyein, an agent a- Furthermore, it also in- FKBP and VMP1, thus
作者 杨光 祝元刚 杨慧
机构地区 吉林省吉林市第二中心医院 首都医科大学北京神经科学研究所北京神经再生与修复研究重点实验室教育部神经变性病重点实验室
出处 《基础医学与临床》 CSCD 北大核心 2008年第12期1336-1338,共3页 Basic and Clinical Medicine
基金 国家重点基础研究发展计划(2006CB500706) 中国高技术研究发展计划(2006AA02A408) 国家自然科学基金(30670655 7042008) 北京市教育委员会科技发展计划项目(KM200610025002) 教育部高等学校博士学科点专项科研基金项目(20060025004) 北京市自然基金面上项目(7082011) 北京市属高等学校人才强教计划资助项目PHR(IHLB)
关键词 自噬 雷帕霉素 神经退行病 帕金森病 autophagy rapamycin neurodegenerative disease therapeutic agent
分类号 R741 [医药卫生—神经病学与精神病学]
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参考文献12

  • 1Hartford CM, Ratain MJ. Rapamycin: Something old, something new, sometimes borrowed and now renewed [J]. Clin Pharmacol Ther, 2007, 82(4) : 381 -388.
  • 2Sarkar S, Perlstein EO, Imarisio S, et al. Small molecules enhance autophagy and reduce toxicity in Huntington's dis- ease models[J]. Nat Chem Biol, 2007, 3(6): 331- 338.
  • 3Rubinsztein DC, Gestwicki JE, Murphy LO, et al. Potential therapeutic applications of autophagy [ J ]. Nat Rev Drug Discov, 2007, 6(4) : 304 -312.
  • 4Rubinsztein DC. The roles of intracellular protein-degradation pathways in neurodegeneration [ J ]. Nature, 2006, 443(7113) : 780 -786
  • 5Donati A. The involvement of macroautophagy in aging andanti-aging interventions[ J]. Mol Aspects Med, 2006, 27 (5 -6) : 455 -470.
  • 6Xiaolin Wan, Helman LJ. The biology behind roTOR inhibition in sarcoma[J]. Oncologist, 2007, 12(8) : 1007 - 1018.
  • 7Cavallini G, Donati A, Taddei M, et al. Evidence for selective mitochondrial autophagy and failure in aging [ J ]. Autophagy, 2007, 3 (1) : 26 - 27.
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  • 9Chen Long, Liu Lei, Luo Yan, et al. MAPK and roTOR pathways are involved in cadmium-induced neuronal apoptosis[J]. J Neurochem, 2008, 105(1):251 -261.
  • 10Holz MK, Ballif BA, Gygi SP, et al. roTOR and S6K1 mediate assembly of the translation preinitiation complex through dynamic protein interchange and ordered phospho- rylation events[J]. Cell, 2005, 123(4): 569-580.

同被引文献23

  • 1Arias R, Sung M, Vasylyev D, et al. Amiloride is neuroprotective in an MPTP model of Parkinson's disease [ J ]. Neurobiol Dis, 2008, 31:334-341.
  • 2Marl Y, Katnik C, Cuevas J. ASICla channels are activated by endogenous protons during ischemia and contribute to synergistic potentiation of intracellular Ca (2+) overload during ischemia and acidosis [ J ]. Cell calcium, 2010, 48: 70 - 82.
  • 3Rabinowitz J, White E. Autophagy and metabolism [ J ]. Science, 2010, 330: 1344- 1348.
  • 4Alvarez-Erviti L, Rodriguez-Oroz M, Cooper J, et al. Chaperone-mediated autophagy markers in Parkinson disease brains[J]. Arch Neurol, 2010, 67: 1464- 1472.
  • 5Wong H, Bauer P, Kurosawa M, et al. Blocking acid-sensing ion channel 1 alleviates Huntington's disease pathology via an ubiquitin-proteasome system-dependent mechanism [J]. Hum Mol Genet, 2008, 17:3223 -3235.
  • 6Xilouri M, Stefanis L. Autophagy in the central nervous system: implications for neurodegenerative disorders [ J ]. CNS Neurol Disord Drug Targets, 2010, 9:701 -719.
  • 7Wang Y, Singh R, Xiang Y, et al. Macroautophagy and chaperone-mediated autophagy are required for hepatocyte resistance to oxidant stress [ J]. Hepatology, 2010, 52: 266 - 277.
  • 8Sidransky E, Nails MA, Aasly JO, et al. Muhicenter anal- ysis of glucocerebrosidase mutations in Parkinson's disease [J]. N EnglJ Med, 2009, 361: 1651-1661.
  • 9Spillantini MG, Sehmidt ML, Lee VM, et al. AlpHA-synu- clein in Lewy bodies[ J]. Nature, 1997,388:839 - 840.
  • 10Tan EK, Tong J, Fook-Chong S, et al. Glucocerebrosidase mutations and risk of Parkinson disease in Chinese patients [J]. Arch Neurol, 2007,64:1056- 1058.

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基础医学与临床
2008年 第12期

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