Department of Chemistry, University of Prishtina, Prishtinë, Kosova.
Faculty of Medicine, University of Prishtina, Prishtinë, Kosova.
Neurosignals. 2021 Mar 31;29(1):14-23. doi: 10.33594/000000352.
The antiaging protein Klotho is encoded by the Klotho gene first identified as an 'aging suppressor', in mice. Klotho deficiency is involved in premature aging and early death, while its overexpression is related to longevity. Klotho is mostly expressed in the kidney, but also in the brain, and in other organs. Two forms of Klotho, the cell membrane and secreted form, have pleiotropic activities that include regulation of general metabolism, oxidative stress, and mineral metabolism that correlates with its effect on accelerating aging. Membrane Klotho serves as an obligate co-receptor for the fibroblast growth factor (FGF), while secreted Klotho plays its role as a humoral factor. Klotho protein participates in the regulation of several biological activities, including regulation of calcium-phosphate homeostasis and PTH as well as vitamin D metabolism. The active form of vitamin D, 1,25(OH)D (1,25-dihydroxy-vitamin D3 = calcitriol), acts as a neurosteroid that participates in the regulation of multiple brain functions. It provides neuroprotection and suppresses oxidative stress, inhibits inflammation and inflammatory mediators, and stimulates various neurotrophins. Calcitriol is involved in many brain-related diseases, including multiple sclerosis, Alzheimer´s disease, Parkinson´s disease, and schizophrenia. This review covers the most recent advances in Klotho research and discusses Klotho-dependent roles of calcitriol in neuro-psycho-pathophysiology.
抗衰老蛋白 Klotho 最初是在小鼠中被鉴定为“衰老抑制剂”的 Klotho 基因编码的。Klotho 缺乏与早衰和早逝有关，而其过表达与长寿有关。Klotho 主要在肾脏中表达，但也在大脑和其他器官中表达。Klotho 有两种形式，即细胞膜形式和分泌形式，具有多种活性，包括调节一般代谢、氧化应激和矿物质代谢，这与其加速衰老的作用有关。细胞膜 Klotho 作为成纤维细胞生长因子 (FGF) 的必需共受体，而分泌型 Klotho 则作为一种体液因子发挥作用。Klotho 蛋白参与调节多种生物学活性，包括钙磷稳态和 PTH 以及维生素 D 代谢的调节。活性维生素 D，1,25(OH)D（1,25-二羟基维生素 D3 = 骨化三醇），作为一种神经甾体，参与调节多种大脑功能。它提供神经保护，抑制氧化应激，抑制炎症和炎症介质，并刺激各种神经营养因子。骨化三醇参与多种与大脑相关的疾病，包括多发性硬化症、阿尔茨海默病、帕金森病和精神分裂症。这篇综述涵盖了 Klotho 研究的最新进展，并讨论了骨化三醇在神经精神病理生理学中的 Klotho 依赖性作用。
