"Is dopamine involved in Alzheimer's disease?".
"Is dopamine involved in Alzheimer's disease?".
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DOI：
10.3389/fnagi.2014.00252
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发表时间：
2014
影响因子：
4.8
通讯作者：
Koch G
中科院分区：
文献类型：
--
作者：
Martorana A;Koch G
阿尔茨海默病（AD）是一种以进行性认知能力下降和痴呆为特征的神经退行性疾病。近年来的研究进展表明，阿尔茨海默病的发病机制似乎比单纯的神经病理学更为复杂。突触可塑性改变、神经元紊乱和细胞死亡是目前公认的阿尔茨海默病的发病机制。人们认为，某些膜蛋白代谢的改变可能导致淀粉样蛋白（Aβ）低聚物的产生，其特征是对神经传递途径具有高度毒性作用，例如由乙酰胆碱介导的神经传递途径。Aβ低聚物与这些神经递质系统的相互作用反过来会诱导细胞功能障碍，神经递质信号不平衡，最终导致神经症状的出现。从这个角度来看，这些机制如何以及是否也可能参与阿尔茨海默病的多巴胺能系统仍然存在争议。最近的实验工作表明，多巴胺能系统很可能与认知能力下降的发生有关，通常可以预测AD的快速进展形式。然而，多巴胺系统在阿尔茨海默病中的作用仍然缺乏明确的认识。在这里，我们回顾了最近支持多巴胺能功能障碍在阿尔茨海默病认知能力下降症状中起致病作用的观点的证据。
Alzheimer's Disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline and dementia. Recent advances indicate that AD pathogenesis appears more complex than its mere neuropathology. Changes in synaptic plasticity, neuronal disarray and cell death are pathways commonly recognized as pathogenic mechanisms of AD. It is thought that the altered metabolism of certain membrane proteins may lead to the production of amyloid (Aβ) oligomers that are characterized by an highly toxic effect on neurotransmission pathways, such as those mediated by Acetylcholine. The interaction of Aβ oligomers with these neurotansmitters systems would in turn induce cell dysfunction, neurotransmitters signaling imbalance and finally lead to the appearance of neurological signs. In this perspective, it is still debated how and if these mechanisms may also engage the dopaminergic system in AD. Recent experimental work revealed that the dopaminergic system may well be involved in the occurrence of cognitive decline, often being predictive of rapidly progressive forms of AD. However, a clear idea on the role of the dopamine system in AD is still missing. Here we review the more recent evidences supporting the notion that the dopaminergic dysfunction has a pathogenic role in cognitive decline symptoms of AD.