Young A B
Neurology Service, Massachusetts General Hospital, Boston 02114.
Res Publ Assoc Res Nerv Ment Dis. 1993;71:175-89.
In summary, EAA play an important role in neurodegenerative disorders simply by virtue of the pathways in brain that utilize EAA as neurotransmitters. Thus, the striatum, which is so strikingly affected in Huntington's disease, receives massive EAAergic input from all regions of the cerebral cortex and from the thalamus. In Parkinson's disease, some of the key pathways projecting into the substantia nigra pars compacta and to the subthalamic nucleus and basal ganglia output zones also use EAA as neurotransmitters. In Alzheimer's disease, the cerebral cortex and hippocampus are dependent on EAAergic neurotransmission for normal function. Drugs that manipulate these neurotransmitter inputs and outputs could be very helpful in the symptomatic relief of all these neurodegenerative disorders. In addition, there may be secondary excitotoxic effects of EAA on neuronal function in neurodegenerative disorders. Genetic abnormalities may render subsets of neurons more vulnerable to changes in ion concentration or energy demands and thus more susceptible to EAA-induced neurotoxicity. Although EAA themselves may not be the primary culprit in a disease, EAA-induced toxicity may cause significant damage as a secondary phenomenon. If so, the neuronal damage could potentially be attenuated by the use of EAA antagonists. Future research on these problems hold great promise.
总之，兴奋性氨基酸（EAA）仅凭借大脑中利用EAA作为神经递质的通路，就在神经退行性疾病中发挥着重要作用。因此，在亨廷顿舞蹈病中受到显著影响的纹状体，接收来自大脑皮层所有区域以及丘脑的大量兴奋性氨基酸能输入。在帕金森病中，一些投射到黑质致密部、底丘脑核和基底神经节输出区的关键通路也使用EAA作为神经递质。在阿尔茨海默病中，大脑皮层和海马体的正常功能依赖于兴奋性氨基酸能神经传递。操纵这些神经递质输入和输出的药物可能对所有这些神经退行性疾病的症状缓解非常有帮助。此外，在神经退行性疾病中，EAA可能对神经元功能产生继发性兴奋毒性作用。基因异常可能使神经元亚群更容易受到离子浓度或能量需求变化的影响，从而更容易受到EAA诱导的神经毒性作用。尽管EAA本身可能不是疾病的主要罪魁祸首，但EAA诱导的毒性可能作为一种继发性现象造成重大损害。如果是这样，使用EAA拮抗剂可能会减轻神经元损伤。对这些问题的未来研究前景广阔。
