Reducing CXCR4 Resulted in Impairing Proliferation and Promoting Aging
Reducing CXCR4 Resulted in Impairing Proliferation and Promoting Aging
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DOI：
10.1007/s12603-018-1013-9
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发表时间：
2018-07-01
影响因子：
5.8
通讯作者：
Wang, R.
中科院分区：
文献类型：
--
作者：
Li, H.;Hao, L.;Wang, R.
阿尔茨海默病（Alzheimer's disease，AD）是一种最常见、最具破坏性的与衰老相关的神经退行性疾病。衰老是一个自然的生理过程，是大脑整体稳态机制的逐渐恶化，伴随着认知能力的下降。趋化因子CXCL 12/CXCR 4信号通路在调节神经系统发育过程和突触可塑性中起着重要作用，本文首次在SH-SY 5 Y细胞模型中证实了CXCR 4在细胞增殖和细胞毒性中的重要作用。本研究首次发现CXCR 4与AKT共定位于细胞膜上，通过调节AKT的活化来防止衰老和AD的发生。总之，我们提供了一条CXCL 12刺激CXCR 4途径调节AKT活化、CREB磷酸化和P53水平从而影响衰老和AD发生的新途径。因此，CXCR 4可能成为AD和衰老诊断和治疗的新靶点和生物标志物。
U Alzheimer's disease (AD) is one of the most common and devastating aging related neurodegenerative diseases. Aging is a natural physiological process, a progressive deterioration of the overall homeostatic brain mechanisms, accompanied by cognitive decline. CXCL12/CXCR4 chemokine signaling plays a critical role in modulating various nervous system developmental processes and in regulating synaptic plasticity.In this article, we have firstly shown that CXCR4 is critical for cell proliferation and cytotoxicity in the SH-SY5Y cell model. Moreover, it has been firstly demonstrated that CXCR4 colocalized with AKT on the membrane and regulated the AKT activation to prevent aging and AD.In a word, we supply a novel pathway that CXCR4 pathway stimulated by CXCL12 regulated AKT activation, CREB phosphorylation and P53 level to affect the process of aging and AD. Therefore, CXCR4 may be a novel target and biomarker for the diagnosis and treatment of AD and aging.