The pathological roles of NDRG2 in Alzheimer's disease, a study using animal models and APPwt‐overexpressed cells

• Published in: CNS neuroscience & therapeutics Vol. 23; no. 8; pp. 667 - 679
• Main Authors: Rong, Xian‐Fang, Sun, Ying‐Ni, Liu, Dong‐Mei, Yin, Hua‐Jing, Peng, Ying, Xu, Shao‐Feng, Wang, Ling, Wang, Xiao‐Liang
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.08.2017; John Wiley and Sons Inc
• Subjects: Adaptor Proteins, Signal Transducing; Aging - metabolism; Alzheimer Disease - metabolism; Alzheimer's disease; Amyloid beta-Peptides - metabolism; Amyloid beta-Protein Precursor - genetics; Amyloid beta-Protein Precursor - metabolism; Animal models; Animals; Apoptosis; Apoptosis - physiology; beta‐amyloid; Brain - metabolism; Caspase; Caspase-8; Cell Line, Tumor; Cell Survival - physiology; Cyclin-dependent kinase 5; Disease Models, Animal; Humans; Male; Mice, Inbred ICR; Mice, Transgenic; Myc protein; NDRG2; Nerve Tissue Proteins - metabolism; Neurodegenerative diseases; Original; Pathology; Peptide Fragments - metabolism; Phosphorylation; Pin1 protein; Presenilin-1 - genetics; Presenilin-1 - metabolism; Proteins - metabolism; Rats, Sprague-Dawley; Stat3 protein; tau phosphorylation; Tau protein; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - metabolism; β-Site APP-cleaving enzyme 1; beta-amyloid; apoptosis; NDRG2; tau phosphorylation; Alzheimer's disease
• ISSN: 1755-5930; 1755-5949
• DOI: 10.1111/cns.12716

Summary Aims To investigate the roles of N‐myc downstream‐regulated gene 2 (NDRG2) in the pathology of aging and neurodegenerative disease such as Alzheimer's disease (AD). Results In this study, we confirmed the upregulation of NDRG2 in the brains of aging and AD animal models. To explore the role of NDRG2 in the pathology of AD at molecular level, we conducted a cell‐based assay of highly expressed wild‐type human APP695 SK‐N‐SH cells (SK‐N‐SH APPwt). By silencing and overexpressing gene of NDRG2, we demonstrated that NDRG2‐mediated increase in Aβ1‐42 was through the pathways of BACE1 and GGA3. NGRG2 improved tau phosphorylation via enhanced activity of CDK5 and decreased Pin1, but it was not affected by GSK3β pathway. NDRG2 might also induce cell apoptosis through the extrinsic (caspase 8) apoptotic pathway by interaction with STAT3. Conclusion Our study confirmed the upregulation of NDRG2 in AD animal models and demonstrated its important roles in AD pathology. NDRG2 might be a potential target for studying and treatment of AD.