Insight Into the Emerging Role of Striatal Neurotransmitters in the Pathophysiology of Parkinson's Disease and Huntington's Disease: A Review.
Insight Into the Emerging Role of Striatal Neurotransmitters in the Pathophysiology of Parkinson's Disease and Huntington's Disease: A Review.
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DOI：
10.2174/1570159x16666180302115032
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发表时间：
2019
影响因子：
5.3
通讯作者：
Kumar P
中科院分区：
文献类型：
--
作者：
Jamwal S;Kumar P
基底节神经递质信号的改变已被一致证明对帕金森病和亨廷顿病的病理生理学基础有显着影响。多巴胺是一种重要的神经递质，在协调身体运动中发挥着至关重要的作用。大脑多巴胺和受体水平的改变从根本上导致不规则运动、谷氨酸介导的兴奋性神经元死亡，并进一步导致其他神经递质水平的不平衡。 GABA、腺苷、乙酰胆碱和内源性大麻素。本综述基于临床和临床前研究的数据，旨在描述各种纹状体神经递质在帕金森病和亨廷顿病发病机制中的作用。此外，我们还收集了基底神经节区域各种神经递质及其代谢物和受体密度变化水平的数据。尽管运动障碍神经病理学的确切机制尚不完全清楚，但与神经递质改变、兴奋性神经元死亡、氧化应激、线粒体功能障碍、神经炎症相关的几种机制正在被提出。恢复神经递质水平和下游信号传导被认为有益于治疗帕金森病和亨廷顿病。因此，迫切需要找到更特异性的药物和药物靶点来恢复大脑中改变的神经递质水平并预防/延缓神经退行性变
Alteration in neurotransmitters signaling in basal ganglia has been consistently shown to significantly contribute to the pathophysiological basis of Parkinson’s disease and Huntington’s disease. Dopamine is an important neurotransmitter which plays a critical role in coordinated body movements. Alteration in the level of brain dopamine and receptor radically contributes to irregular movements, glutamate mediated excitotoxic neuronal death and further leads to imbalance in the levels of other neurotransmitters viz. GABA, adenosine, acetylcholine and endocannabinoids. This review is based upon the data from clinical and preclinical studies to characterize the role of various striatal neurotransmitters in the pathogenesis of Parkin-son’s disease and Huntington’s disease. Further, we have collected data of altered level of various neurotransmitters and their metabolites and receptor density in basal ganglia region. Although the exact mechanisms underlying neuropathology of movement disorders are not fully understood, but several mechanisms related to neurotransmitters alteration, excitotoxic neu-ronal death, oxidative stress, mitochondrial dysfunction, neuroinflammation are being put forward. Restoring neurotransmit-ters level and downstream signaling has been considered to be beneficial in the treatment of Parkinson’s disease and Hun-tington’s disease. Therefore, there is an urgent need to identify more specific drugs and drug targets that can restore the al-tered neurotransmitters level in brain and prevent/delay neurodegeneration