Alexi T, Hughes P E, Faull R L, Williams C E
Research Centre for Developmental Medicine and Biology, School of Medicine, Starship Hospital, University of Auckland, New Zealand.
Neuroreport. 1998 Aug 3;9(11):R57-64. doi: 10.1097/00001756-199808030-00001.
3-Nitropropionic acid (3-NP) is a mitochondrial toxin which interferes with ATP synthesis. Accidental ingestion of 3-NP by humans as well as other mammals results in neuronal degeneration within the basal ganglia and movement dysfunction characterized by dystonia, chorea, and hypokinesia. The selective degeneration of structures of the basal ganglia occurs despite the non-selective impairment of energy metabolism throughout the brain and body. These effects of 3-NP are shared with the genetic disorder Huntington's disease (HD), which is characterized by progressive neurodegeneration of the basal ganglia and choreic motor dysfunction. These similarities have prompted further investigation of 3-NP as an animal model of HD. Metabolic compromise with 3-NP causes neurodegeneration that involves three interacting processes: energy impairment, excitotoxicity, and oxidative stress. This triplet of cooperative pathways of neurodegeneration helps to explain 3-NP's regional selectivity of neurotoxicity to the basal ganglia. This mini-review will focus on the actions of 3-NP and the related compound, malonic acid (MA), in the central nervous system, with an emphasis on the more current findings regarding their mechanisms of action.
3-硝基丙酸（3-NP）是一种干扰ATP合成的线粒体毒素。人类以及其他哺乳动物意外摄入3-NP会导致基底神经节内的神经元变性以及以肌张力障碍、舞蹈症和运动迟缓为特征的运动功能障碍。尽管大脑和身体的能量代谢受到非选择性损害，但基底神经节结构仍会发生选择性退化。3-NP的这些作用与遗传性疾病亨廷顿舞蹈症（HD）相同，后者的特征是基底神经节进行性神经变性和舞蹈样运动功能障碍。这些相似之处促使人们进一步研究将3-NP作为HD的动物模型。3-NP导致的代谢损害会引起神经变性，这涉及三个相互作用的过程：能量损伤、兴奋性毒性和氧化应激。这种神经变性的三联协同途径有助于解释3-NP对基底神经节神经毒性的区域选择性。这篇综述将重点关注3-NP和相关化合物丙二酸（MA）在中枢神经系统中的作用，重点是关于它们作用机制的最新研究结果。
