RPS23RG1 reduces Aβ oligomer-induced synaptic and cognitive deficits

• Published in: Scientific reports 2016-01, Vol.6 (1), p.18668-18668, Article 18668
• Main Authors: Yan, Li, Chen, Yaomin, Li, Wubo, Huang, Xiumei, Badie, Hedieh, Jian, Fan, Huang, Timothy, Zhao, Yingjun, Cohen, Stanley N., Li, Limin, Zhang, Yun-wu, Luo, Huanmin, Tu, Shichun, Xu, Huaxi
• Format: Article
• Language: English
• Subjects: 13/1; 13/109; 13/89; 13/95; 14/63; 45; 631/378/1689/1283; 631/80/304; Adenylyl Cyclases - metabolism; Alzheimer Disease - genetics; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer Disease - physiopathology; Amyloid beta-Peptides - metabolism; Animals; Base Sequence; CA1 Region, Hippocampal - metabolism; CA1 Region, Hippocampal - pathology; Cloning, Molecular; Cognitive Dysfunction - genetics; Cognitive Dysfunction - metabolism; Cognitive Dysfunction - pathology; Cognitive Dysfunction - physiopathology; Cyclic AMP-Dependent Protein Kinases - metabolism; Disease Models, Animal; Gene Expression Regulation; Gene Knockdown Techniques; Humanities and Social Sciences; Humans; Long-Term Potentiation - genetics; Mice; Mice, Transgenic; multidisciplinary; Neuronal Plasticity; Neurons - metabolism; Phosphorylation; Protein Aggregates; Protein Aggregation, Pathological - metabolism; Protein Binding; Ribosomal Proteins - chemistry; Ribosomal Proteins - genetics; Ribosomal Proteins - metabolism; RNA, Messenger - genetics; Science; Synapses - metabolism; tau Proteins - genetics; tau Proteins - metabolism
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep18668

Alzheimer’s disease (AD) is the most common form of dementia in the elderly. It is generally believed that β-amyloidogenesis, tau-hyperphosphorylation and synaptic loss underlie cognitive decline in AD. Rps23rg1 , a functional retroposed mouse gene, has been shown to reduce Alzheimer’s β-amyloid (Aβ) production and tau phosphorylation. In this study, we have identified its human homolog and demonstrated that RPS23RG1 regulates synaptic plasticity, thus counteracting Aβ oligomer (oAβ)-induced cognitive deficits in mice. The level of RPS23RG1 mRNA is significantly lower in the brains of AD compared to non-AD patients, suggesting its potential role in the pathogenesis of the disease. Similar to its mouse counterpart, human RPS23RG1 interacts with adenylate cyclase, activating PKA/CREB and inhibiting GSK-3. Furthermore, we show that human RPS23RG1 promotes synaptic plasticity and offsets oAβ-induced synaptic loss in a PKA-dependent manner in cultured primary neurons. Overexpression of Rps23rg1 in transgenic mice consistently prevented oAβ-induced PKA inactivation, synaptic deficits, suppression of long-term potentiation and cognitive impairment as compared to wild type littermates. Our study demonstrates that RPS23RG1 may reduce the occurrence of key elements of AD pathology and enhance synaptic functions to counteract oAβ-induced synaptic and cognitive deficits in AD.