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Can I read Osteocyte-derived sclerostin impairs cognitive function during ageing and Alzheimer’s disease progression on EtoBox?
Osteocyte-derived sclerostin impairs cognitive function during ageing and Alzheimer’s disease progression by Tianshu Shi; Siyu Shen; Yong Shi; Qianjin Wang; Guanqun Zhang; Jiaquan Lin; Jiang Chen; Feng Bai; Lei Zhang; Yangyufan Wang; Wang Gong; Xiaoyan Shao; Guiquan Chen; Wenjin Yan; Xiang Chen; Yuze Ma; Liming Zheng; Jianghui Qin; Ke Lu; Na Liu; Yun Xu; Yun Stone Shi; Qing Jiang; Baosheng Guo is a Medicine article available to read on EtoBox.
What is Osteocyte-derived sclerostin impairs cognitive function during ageing and Alzheimer’s disease progression about?
Ageing increases susceptibility t o n eu ro de ge ne rative disorders, such as Alzheimer's disease (AD). Serum levels of sclerostin, an osteocyte-derived Wnt-β-catenin signalling antagonist, increase with age and inhibit o st eobl as to ge nesis. As Wnt-β-catenin signalling acts as a protective mechanism for memory, we hypothesize that osteocyte-derived sclerostin can impact cognitive function under pathological conditions. Here we show that osteocyte-derived sclerostin can cross the blood-brain barrier of old mice, where it can dysregulate Wnt-β-catenin signalling. Gain-of-function and loss-of-function experiments show that abnormally elevated osteocyte-derived sclerostin impairs synaptic plasticity and memory in old mice of both sexes. Mechanistically, sclerostin increases amyloid β (Aβ) production through β-catenin-β-secretase 1 (BACE1) signalling, indicating a functional role for sclerostin in AD. Accordingly, high sclerostin levels in patients with AD of both sexes are associated with severe cognitive impairment, which is in line with the acceleration of Αβ production in an AD mouse model with bone-specific overexpression of sclerostin. Thus, we demonstrate osteocyte-derived s
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- Author
- Tianshu Shi; Siyu Shen; Yong Shi; Qianjin Wang; Guanqun Zhang; Jiaquan Lin; Jiang Chen; Feng Bai; Lei Zhang; Yangyufan Wang; Wang Gong; Xiaoyan Shao; Guiquan Chen; Wenjin Yan; Xiang Chen; Yuze Ma; Liming Zheng; Jianghui Qin; Ke Lu; Na Liu; Yun Xu; Yun Stone Shi; Qing Jiang; Baosheng Guo
- Publisher
- Springer Science and Business Media LLC
- Published
- 2024
- Language
- EN
- Field
- Medicine (Life Sciences)