Parkinson's disease (PD) and Alzheimer's disease (AD) are the most common chronic neurodegenerative disorders, characterized by motoric dysfunction or cognitive decline in the early stage, respectively, but often by both symptoms in the advanced stage. Among underlying molecular pathologies that PD and AD patients have in common, more attention is recently paid to the central metabolic dysfunction presented as insulin resistant brain state (IRBS) and altered cerebral glucose metabolism, both also explored in animal models of these diseases. This review aims to compare IRBS and alterations in cerebral glucose metabolism in representative non-transgenic animal PD and AD models. The comparison is based on the selectivity of the neurotoxins which cause experimental PD and AD, towards the cellular membrane and intracellular molecular targets as well as towards the selective neurons/non-neuronal cells, and the particular brain regions. Mitochondrial damage and co-expression of insulin receptors, glucose transporter-2 and dopamine transporter on the membrane of particular neurons as well as astrocytes seem to be the key points which are further discussed in a context of alterations in insulin signalling in the brain and its interaction with dopaminergic transmission, particularly regarding the time frame of the experimental AD/PD pathology appearance and the correlation with cognitive and motor symptoms. Such a perspective provides evidence on IRBS being a common underlying metabolic pathology and a contributor to neurodegenerative processes in representative non-transgenic animal PD and AD models, instead of being a direct cause of a particular neurodegenerative disorder.

中文翻译：

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非阿尔茨海默氏病和帕金森氏病非转基因动物模型中共有的脑代谢病理学。

帕金森氏病（PD）和阿尔茨海默氏病（AD）是最常见的慢性神经退行性疾病，其特征分别是早期的运动功能障碍或认知功能减退，但往往以晚期的两种症状为特征。在PD和AD患者共有的潜在分子病理学中，最近更加关注以胰岛素抵抗性脑状态（IRBS）和脑葡萄糖代谢改变为中心的中枢代谢功能障碍，这两种疾病的动物模型中也都进行了探讨。本文旨在比较代表性的非转基因动物PD和AD模型中IRBS和脑葡萄糖代谢的变化。比较是基于导致实验性PD和AD的神经毒素的选择性，朝向细胞膜和细胞内分子靶标以及选择性神经元/非神经元细胞和特定的大脑区域。线粒体损伤和特定神经元以及星形胶质细胞膜上胰岛素受体，葡萄糖转运蛋白2和多巴胺转运蛋白的共表达似乎是关键点，在大脑及其脑中胰岛素信号传导变化的背景下将进一步讨论这些关键点与多巴胺能传递的相互作用，特别是关于实验性AD / PD病理学表现的时间范围以及与认知和运动症状的相关性。这种观点为IRBS提供了证据，表明IRBS是代表性的非转基因动物PD和AD模型中常见的基础代谢病理学和神经退行性过程的贡献者，