中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2017, Vol. 12 ›› Issue (4): 534-537.doi: 10.4103/1673-5374.205082

• 综述:退行性病与再生 • 上一篇    下一篇

磷脂酰丝氨酸通过抑制HDAC改善轴突运输：具有治疗神经退行性疾病的潜力吗？

  

  • 收稿日期:2017-03-20 出版日期:2017-04-15 发布日期:2017-04-15
  • 基金资助:

    此项研究由自主神经障碍基金会、以色列科学基金会（ISF）[142/13，1439/14]、Teva制药工业有限公司所属的以色列国家神经科学卓越网（NNE）[1234944]、欧洲研究委员会（ERC）[309377]共同赞助

Phosphatidylserine improves axonal transport by inhibition of HDAC and has potential in treatment of neurodegenerative diseases

Shiran Naftelberg1, Gil Ast1, Eran Perlson2   

  1. 1 Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; 2 Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
  • Received:2017-03-20 Online:2017-04-15 Published:2017-04-15
  • Contact: Gil Ast, Ph.D. or Eran Perlson, Ph.D., gilast@post.tau.ac.il or eranpe@post.tau.ac.il.
  • Supported by:

    Funding for this work was provided by grants from the Dysautonomia Foundation. Israel Science Foundation (ISF) [142/13, 1439/14], and by Teva Pharmaceutical Industries Ltd as part of the Israeli National Network of Excellence in Neuroscience (NNE) [1234944]. E.P. was supported by grants from the Israel Science Foundation (ISF) [561/11]; and the European Research Council (ERC) [309377]. S.N. was supported by grants from Teva Pharmaceutical Industries Ltd. under the Israeli National Network of Excellence in Neuroscience.

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摘要：

 

家族性自主神经障碍（FD）是一种罕见的儿童神经变性疾病，由于IKBKAP基因中的点突变导致IKAP蛋白质产生减少引发。该疾病主要影响背根神经节（DRG）和交感神经节。文章研究发现，FD患者的神经退行性疾病的分子机制是神经生长因子的轴突运输和微管稳定在DRG中存在缺陷。神经元是具有极长轴突的高度极化细胞。为了存活和维持适当功能，神经元依赖于蛋白质和其他细胞组分从神经元身体沿轴突转运。文中进一步证明了IKAP对轴突维护是必需的，并表明磷脂酰丝氨酸作为HDAC6抑制剂具有挽救FD细胞的神经元功能。本文将重点强调一些最新研究成果。

ORCID:0000-0001-6047-9613(Eran Perlson)

Abstract:

Familial dysautonomia (FD) is a rare children neurodegenerative disease caused due to a point mutation in the IKBKAP gene that results in decreased IKK complex-associated protein (IKAP) protein production. The disease affects mostly the dorsal root ganglion (DRG) and the sympathetic ganglion. Recently, we found that the molecular mechanisms underlying neurodegeneration in FD patients are defects in axonal transport of nerve growth factors and microtubule stability in the DRG. Neurons are highly polarized cells with very long axons. In order to survive and maintain proper function, neurons depend on transport of proteins and other cellular components from the neuronal body along the axons. We further demonstrated that IKAP is necessary for axon maintenance and showed that phosphatidylserine acts as an HDAC6 inhibitor to rescue neuronal function in FD cells. In this review, we will highlight our latest research findings.

Key words: axonal transport, neurodegeneration, microtubule, familial dysautonomia, phosphatidylserine, HDAC6