School of Pharmacy and Emerging Sciences, Baddi University of Emerging Sciences & Technology, Baddi, Solan, India.
Department of Pharmaceutical Sciences and Technology, Maharaja Ranjit Singh Punjab Technical University, Bathinda, Panjab, India.
Curr Neuropharmacol. 2019;17(2):165-175. doi: 10.2174/1570159X16666180302115032.
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 Parkinson'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 neuronal death, oxidative stress, mitochondrial dysfunction, neuroinflammation are being put forward. Restoring neurotransmitters level and downstream signaling has been considered to be beneficial in the treatment of Parkinson's disease and Huntington's disease. Therefore, there is an urgent need to identify more specific drugs and drug targets that can restore the altered neurotransmitters level in brain and prevent/delay neurodegeneration.
基底神经节中神经递质信号的改变被一致证明对帕金森病和亨廷顿病的病理生理基础有重要贡献。多巴胺是一种重要的神经递质,在协调身体运动中起着关键作用。大脑多巴胺和受体水平的改变极大地导致了不规则运动、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(如 GABA、腺苷、乙酰胆碱和内源性大麻素)水平失衡。本综述基于临床和临床前研究的数据,描述了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改变的相关数据。虽然运动障碍神经病理学的确切机制尚未完全阐明,但目前提出了几种与神经递质改变、兴奋性神经元死亡、氧化应激、线粒体功能障碍、神经炎症相关的机制。恢复神经递质水平和下游信号转导被认为对治疗帕金森病和亨廷顿病有益。因此,迫切需要确定更具特异性的药物和药物靶点,以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。