中国神经再生研究(英文版) ›› 2015, Vol. 10 ›› Issue (12): 1928-1929.doi: 10.4103/1673-5374.169631

• 观点:神经损伤修复保护与再生 • 上一篇    下一篇

肌醇代谢途径可能是神经保护策略的靶标?

  

  • 收稿日期:2015-10-26 出版日期:2015-12-30 发布日期:2015-12-30

The inositol metabolism pathway as a target for neuroprotective strategies

Arne M. Nystuen* , Andy W. Yang   

  1. Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE, USA (Nystuen AM, Yang AW)
    Currently at Neurotech, Inc., Cumberland, RI, USA (Nystuen AM)
  • Received:2015-10-26 Online:2015-12-30 Published:2015-12-30
  • Contact: Arne M. Nystuen, Ph.D.,arne.nystuen@gmail.com.

摘要:

神经元的渐进性和永久损失即通常所说的神经退变,是临床上不同病状反射影响神经元功能的一系列遗传异质性疾病的表型特征。退变通常会导致功能衰弱进而损失,即使是健康人群也不能幸免,其中神经退行性疾病直接耗费了巨大的医疗费用,有人估计该类疾病如阿尔茨海默病患者每年的医疗费用超过36000美元。目前仍然缺少有效的治疗方法,以阻止这些疾病患者神经元的不可逆性死亡。但越来越多的证据表明,一种可能的神经保护策略是以肌醇1,4,5-三磷酸途径调节为靶标来阻止神经细胞内多余的钙储存释放。文章主要回顾了基于可溶性肌醇1,4,5-三磷酸途径的神经保护策略。因为神经退变的原因是多种多样的,多种疾病之间可能存在共同的病理通路,因此保护共同分子途径靶向或许会成为治疗该类疾病的研究方向。

Abstract:

The progressive and permanent loss of neurons that is commonly referred to as neurodegeneration is a phenotypic characteristic of a large group of genetically heterogeneous diseases with clinically distinct pathologies reflective of the function of the neuron affected. Degeneration typically results in a debilitating loss of function inan otherwise healthy person. Neurodegenerative diseases have enormous direct health care costs, with some estimates for diseases, such as Alzheimer’s exceeding $36,000 per patient annually. Currently there is a lack of effective treatments for neurodegenerative disease, thus there is no way to slow or prevent the irreversible death of neurons in patients suffering from these diseases. Growing evidence suggests that the pathways controlling the levels of intracellular calcium [Ca2+]i, including the second messenger inositol 1,4,5-trisphosphate (InsP3), are disrupted in some of the more common forms of neurodegeneration. Dysfunction in these pathway allow for excessive, toxic levels of [Ca2+]i to accumulate. One possible neuroprotective strategy would be to target InsP3 regulatory pathways to prevent excess calcium release from intracellular stores. This review will focus on the current strategies of neuroprotection that involve the soluble InsP3 pathways. While the causes of neurodegeneration are diverse, common pathological pathways may exist between diseases, protective targeting of a common pathway would have the potential to treat genetically distinct diseases.