Division of Ultrastructural Research, Wroclaw Medical University, 50-368, Wroclaw, Poland.
Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolfa Weigla 12, 53-114, Wroclaw, Poland.
Geroscience. 2024 Feb;46(1):71-85. doi: 10.1007/s11357-023-00923-1. Epub 2023 Aug 30.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder and is the most common cause of dementia. The pathogenesis of AD still remains unclear, including two main hypotheses: amyloid cascade and tau hyperphosphorylation. The hallmark neuropathological changes of AD are extracellular deposits of amyloid-β (Aβ) plaques and intracellular neurofibrillary tangles (NFTs). Endocytosis plays an important role in a number of cellular processes including communication with the extracellular environment, nutrient uptake, and signaling by the cell surface receptors. Based on the results of genetic and biochemical studies, there is a link between neuronal endosomal function and AD pathology. Taking this into account, we can state that in the results of previous research, endolysosomal abnormality is an important cause of neuronal lesions in the brain. Endocytosis is a central pathway involved in the regulation of the degradation of amyloidogenic components. The results of the studies suggest that a correlation between alteration in the endocytosis process and associated protein expression progresses AD. In this article, we discuss the current knowledge about endosomal abnormalities in AD.
阿尔茨海默病（AD）是一种进行性神经退行性疾病，是痴呆症最常见的病因。AD 的发病机制仍不清楚，包括两个主要假说：淀粉样蛋白级联和 tau 过度磷酸化。AD 的标志性神经病理学变化是细胞外淀粉样β（Aβ）斑块的沉积和细胞内神经原纤维缠结（NFTs）。内吞作用在许多细胞过程中起着重要作用，包括与细胞外环境的通讯、营养物质的摄取以及细胞表面受体的信号转导。基于遗传和生化研究的结果，神经元内体功能与 AD 病理学之间存在联系。考虑到这一点，我们可以说，在之前的研究结果中，内体溶酶体异常是大脑神经元损伤的重要原因。内吞作用是调节淀粉样蛋白成分降解的核心途径。研究结果表明，内吞作用过程的改变与相关蛋白表达的改变与 AD 的进展相关。在本文中，我们讨论了 AD 中内体异常的现有知识。
