GPNMB mitigates Alzheimer's disease and enhances autophagy via suppressing the mTOR signal. (10th January 2022)

• Record Type: Journal Article
• Authors: Zhu, Zhongkang; Liu, Yuxi; Li, Xinyun; Zhang, Lin; Liu, Huihui; Cui, Yong; Wang, Yanjie; Zhao, Danyu
• Is Part Of: Neuroscience letters. Volume 767(2022)
• Publication Date: 2022-01-10
• Subjects: Alzheimer's disease -- GPNMB -- Autophagy -- mTOR -- Amyloid beta; Neurology -- Periodicals; Neurology -- Periodicals; Research -- Periodicals; Neurologie -- Périodiques; Neuroanatomie -- Périodiques; Neuropharmacologie -- Périodiques; Neurophysiologie -- Périodiques; Neurology; Periodicals; Electronic journals; 617.48
• DOI: 10.1016/j.neulet.2021.136300
• Languages: English
• ISSNs: 0304-3940

Abstract

Highlights: GPNMB was highly expressed in the hippocampus of APP/PS1 mice. GPNMB improved cognitive impairment through enhancing amyloid beta clearance. GPNMB enhanced autophagy via repressing the mTOR signal. Abstract: 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.