Reducing CXCR4 Resulted in Impairing Proliferation and Promoting Aging.

BACKGROUND: 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.

RESULTS: 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.

DISCUSSION: 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.