A Functional Mouse Retroposed Gene Rps23r1 Reduces Alzheimer's Beta-amyloid Levels and Tau Phosphorylation

Overview

Journal Neuron

Publisher Cell Press

Specialty Neurology

Date 2009 Nov 17

PMID 19914182

Citations 22

Authors

Yun-Wu Zhang

Shijie Liu

Xue Zhang

Wu-Bo Li

Yaomin Chen

Xiumei Huang

Liangwu Sun

Wenjie Luo

William J Netzer

Richard Threadgill

Gordon Wiegand

Ruishan Wang

Stanley N Cohen

Paul Greengard

Francesca-Fang Liao

Limin Li

Huaxi Xu

Affiliations

Soon will be listed here.

Abstract

Senile plaques consisting of beta-amyloid (Abeta) and neurofibrillary tangles composed of hyperphosphorylated tau are major pathological hallmarks of Alzheimer's disease (AD). Elucidation of factors that modulate Abeta generation and tau hyperphosphorylation is crucial for AD intervention. Here, we identify a mouse gene Rps23r1 that originated through retroposition of ribosomal protein S23. We demonstrate that RPS23R1 protein reduces the levels of Abeta and tau phosphorylation by interacting with adenylate cyclases to activate cAMP/PKA and thus inhibit GSK-3 activity. The function of Rps23r1 is demonstrated in cells of various species including human, and in transgenic mice overexpressing RPS23R1. Furthermore, the AD-like pathologies of triple transgenic AD mice were improved and levels of synaptic maker proteins increased after crossing them with Rps23r1 transgenic mice. Our studies reveal a new target/pathway for regulating AD pathologies and uncover a retrogene and its role in regulating protein kinase pathways.

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