GPNMB mitigates Alzheimer’s disease and enhances autophagy via suppress‐ ing the mTOR signal
GPNMB mitigates Alzheimer’s disease and enhances autophagy via suppress‐ ing the mTOR signal
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GPNMB 通过抑制 mTOR 信号减轻阿尔茨海默病并增强自噬
DOI：
10.1016/j.neulet.2021.136300
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发表时间：
2022
影响因子：
2.5
通讯作者：
赵丹玉
中科院分区：
文献类型：
--
作者：
朱仲康;刘羽茜;李新云;张林;刘慧慧;崔勇;王艳杰;赵丹玉
阿尔茨海默病（AD）是一种常见的神经退行性疾病，其特征是β淀粉样蛋白（a β）积累。我们发现糖蛋白NMB （GPNMB）在AD小鼠模型APP/PS1小鼠脑中高表达。然而，它在AD中的作用仍不清楚。在本研究中，我们旨在探讨GPNMB在AD中的功能。采用免疫荧光和western blot检测GPNMB在脑组织中的表达。此外，通过功能获得探索GPNMB在AD中的作用。通过透射电镜和beclin-1免疫荧光观察自噬对Aβ清除的影响。此外，采用自噬抑制剂3-MA来证明GPNMB是否通过自噬降低了Aβ水平。我们发现过表达GPNMB可改善APP/PS1小鼠的ad样行为，并减少Aβ沉积。进一步研究表明，GPNMB可增强自噬，减少小胶质细胞，抑制mTOR信号的激活。此外，3-MA治疗消除了GPNMB对Aβ清除的有益作用。本研究表明，AD脑组织中高水平的GPNMB可能通过抑制mTOR信号增强自噬，从而帮助清除Aβ，改善AD样行为。GPNMB的这种有益作用为我们提供了预防和治疗AD的新策略。
Alzheimer’s disease (AD) is a common neurodegenerative disease which is characterized by amyloid beta (Aβ) accumulation. We found that glycoprotein NMB (GPNMB) was highly expressed in the brain of APP/PS1 mice, a mouse model of AD. However, its role in AD remains unclear. In this study, we aimed to explore the function of GPNMB in AD. The expression of GPNMB in the brain was detected by immunofluorescence and western blot. In addition, the role of GPNMB in AD was explored through gain-of-function. Autophagy, which is beneficial to Aβ clearance, was evaluated by transmission electron microscope and immunofluorescence with beclin-1. Furthermore, 3-MA, an autophagy inhibitor, was employed to evidence whether GPNMB reduced the level of Aβ through autophagy. We found that over-expression of GPNMB improved AD-like behaviors in APP/PS1 mice and reduced Aβ deposition. Further study showed that GPNMB enhanced autophagy, reduced microglial cells and inhibited the activation of the mTOR signal. Additionally, treatment with 3-MA abolished the beneficial effect of GPNMB on Aβ clearance. This study revealed that the high level of GPNMB in AD brain may help Aβ clearance and improve AD-like behaviors through enhancing autophagy via suppressing the mTOR signal. This beneficial role of GPNMB provides us novel strategies for the prevention and treatment of AD.