A functional mouse retroposed gene Rps23r1 reduces Alzheimer's beta-amyloid levels and tau phosphorylation.

Neuron
Yun-wu ZhangHuaxi Xu

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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Citations

Oct 16, 2012·Molecular Biology and Evolution·Joanna CiomborowskaIzabela Makałowska
Jul 24, 2010·Genome Research·Henrik Kaessmann
Jun 20, 2012·Molecular Neurodegeneration·Yonghao ZhaoYun-wu Zhang
Aug 20, 2010·International Journal of Alzheimer's Disease·Thorsten KoechlingJesus Avila
Jul 5, 2011·Annual Review of Genomics and Human Genetics·Chris P PontingStephen Meader
Apr 28, 2010·Expert Review of Neurotherapeutics·Jesús AvilaFélix Hernández
Jan 7, 2016·Scientific Reports·Li YanHuaxi Xu
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Sep 11, 2020·Cell Death and Differentiation·Dongdong ZhaoYun-Wu Zhang
Jan 23, 2021·Life·Klaudia Staszak, Izabela Makałowska
May 3, 2019·Cell Reports·Carole DeytsAngèle T Parent

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