Department of Biotechnology, Institute of Biology and Biotechnology, Collegium Scientarium Naturalium, University of Rzeszow, Werynia, Poland.
Vitam Horm. 2022;118:223-246. doi: 10.1016/bs.vh.2021.12.001. Epub 2022 Jan 17.
Klotho gene was originally recognized as a putative aging-suppressor and its prominent age-regulating effects are mostly attributed to the modulation of mineral homeostasis in the kidney. However, recent studies link alterations in hippocampal Klotho expression with cognitive impairment and neurodegenerative diseases. This suggests that hippocampal neurons require Klotho for health and proper functionality. Klotho protects against neuronal dysfunction and regulates several intracellular signaling pathways including oxidative stress response, inflammation, DNA damage, autophagy, endoplasmic reticulum stress response, and multiple types of cell death. Specifically, this chapter covers the current knowledge as to how Klotho protein affects the hippocampal neuronal cells, with special attention paid to underlying molecular mechanisms, and thus influences hippocampal development, hippocampal-dependent cognition, behavior, and motor skills as well as mediates neurodegenerative processes.
Klotho 基因最初被认为是一种潜在的衰老抑制剂，其显著的年龄调节作用主要归因于肾脏中矿物质稳态的调节。然而，最近的研究将海马体 Klotho 表达的改变与认知障碍和神经退行性疾病联系起来。这表明海马神经元需要 Klotho 来保持健康和正常功能。Klotho 可防止神经元功能障碍，并调节几种细胞内信号通路，包括氧化应激反应、炎症、DNA 损伤、自噬、内质网应激反应和多种类型的细胞死亡。具体来说，本章涵盖了目前关于 Klotho 蛋白如何影响海马神经元细胞的知识，特别关注潜在的分子机制，从而影响海马体发育、海马体依赖的认知、行为和运动技能，并介导神经退行性过程。
