Alexi T, Borlongan C V, Faull R L, Williams C E, Clark R G, Gluckman P D, Hughes P E
Research Centre for Developmental Medicine and Biology, School of Medicine, University of Auckland, New Zealand.
Prog Neurobiol. 2000 Apr;60(5):409-70. doi: 10.1016/s0301-0082(99)00032-5.
There are three main mechanisms of neuronal cell death which may act separately or cooperatively to cause neurodegeneration. This lethal triplet of metabolic compromise, excitotoxicity, and oxidative stress causes neuronal cell death that is both necrotic and apoptotic in nature. Aspects of each of these three mechanisms are believed to play a role in the neurodegeneration that occurs in both Parkinson's and Huntington's diseases. Strategies to rescue or protect injured neurons usually involve promoting neuronal growth and function or interfering with neurotoxic processes. Considerable research has been done on testing a large array of neuroprotective agents using animal models which mimic these disorders. Some of these approaches have progressed to the clinical arena. Here, we review neuroprotective strategies which have been found to successfully ameliorate the neurodegeneration associated with Parkinson's and Huntington's diseases. First, we will give an overview of the mechanisms of cell death and the background of Parkinson's and Huntington's diseases. Then we will elaborate on a range of neuroprotective strategies, including neurotrophic factors, anti-excitotoxins, antioxidants, bioenergetic supplements, anti-apoptotics, immunosuppressants, and cell transplantation techniques. Most of these approaches hold promise as potential therapies in the treatment of these disorders.
神经元细胞死亡有三种主要机制,它们可能单独或协同作用导致神经退行性变。这种由代谢紊乱、兴奋性毒性和氧化应激组成的致命三联征会导致神经元细胞死亡,其本质上既有坏死又有凋亡。这三种机制的各个方面都被认为在帕金森病和亨廷顿病中发生的神经退行性变中起作用。拯救或保护受损神经元的策略通常包括促进神经元生长和功能或干扰神经毒性过程。已经进行了大量研究,使用模拟这些疾病的动物模型来测试一系列神经保护剂。其中一些方法已经进入临床领域。在这里,我们回顾了已被发现能成功改善与帕金森病和亨廷顿病相关的神经退行性变的神经保护策略。首先,我们将概述细胞死亡机制以及帕金森病和亨廷顿病的背景。然后我们将详细阐述一系列神经保护策略,包括神经营养因子、抗兴奋性毒素、抗氧化剂、生物能量补充剂、抗凋亡剂、免疫抑制剂和细胞移植技术。这些方法中的大多数有望成为治疗这些疾病的潜在疗法。