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神经递质受体与阿尔茨海默病和帕金森病的认知功能障碍。

Neurotransmitter receptors and cognitive dysfunction in Alzheimer's disease and Parkinson's disease.

机构信息

Department of Neurology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510630, PR China.

出版信息

Prog Neurobiol. 2012 Apr;97(1):1-13. doi: 10.1016/j.pneurobio.2012.02.002. Epub 2012 Feb 25.

Abstract

Cognitive dysfunction is one of the most typical characteristics in various neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease (advanced stage). Although several mechanisms like neuronal apoptosis and inflammatory responses have been recognized to be involved in the pathogenesis of cognitive dysfunction in these diseases, recent studies on neurodegeneration and cognitive dysfunction have demonstrated a significant impact of receptor modulation on cognitive changes. The pathological alterations in various receptors appear to contribute to cognitive impairment and/or deterioration with correlation to diversified mechanisms. This article recapitulates the present understandings and concepts underlying the modulation of different receptors in human beings and various experimental models of Alzheimer's disease and Parkinson's disease as well as a conceptual update on the underlying mechanisms. Specific roles of serotonin, adrenaline, acetylcholine, dopamine receptors, and N-methyl-D-aspartate receptors in Alzheimer's disease and Parkinson's disease will be interactively discussed. Complex mechanisms involved in their signaling pathways in the cognitive dysfunction associated with the neurodegenerative diseases will also be addressed. Substantial evidence has suggested that those receptors are crucial neuroregulators contributing to cognitive pathology and complicated correlations exist between those receptors and the expression of cognitive capacities. The pathological alterations in the receptors would, therefore, contribute to cognitive impairments and/or deterioration in Alzheimer's disease and Parkinson's disease. Future research may shed light on new clues for the treatment of cognitive dysfunction in neurodegenerative diseases by targeting specific alterations in these receptors and their signal transduction pathways in the frontal-striatal, fronto-striato-thalamic, and mesolimbic circuitries.

摘要

认知功能障碍是阿尔茨海默病和帕金森病等各种神经退行性疾病(晚期)的最典型特征之一。尽管已经认识到神经元凋亡和炎症反应等几种机制参与了这些疾病认知功能障碍的发病机制,但最近对神经退行性变和认知功能障碍的研究表明,受体调节对认知变化有重大影响。各种受体的病理改变似乎与多种机制相关,导致认知障碍和/或恶化。本文综述了人类和各种阿尔茨海默病和帕金森病实验模型中不同受体调制的现有认识和概念,以及潜在机制的概念更新。将互动讨论 5-羟色胺、肾上腺素、乙酰胆碱、多巴胺受体和 N-甲基-D-天冬氨酸受体在阿尔茨海默病和帕金森病中的特定作用。还将涉及它们在与神经退行性疾病相关的认知功能障碍的信号通路中的复杂机制。大量证据表明,这些受体是导致认知病理学的关键神经调节剂,并且这些受体与认知能力的表达之间存在复杂的相关性。因此,受体的病理改变会导致阿尔茨海默病和帕金森病中的认知障碍和/或恶化。未来的研究可能会通过针对这些受体及其在额纹状体、额纹状体丘脑和中边缘回路中的信号转导通路的特定改变,为神经退行性疾病中认知功能障碍的治疗提供新的线索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35cb/3371373/615b995c581e/nihms360508f1.jpg

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