Reducing CXCR4 Resulted in Impairing Proliferation and Promoting Aging

J Nutr Health Aging. 2018;22(7):785-789. doi: 10.1007/s12603-018-1013-9.

Abstract

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.

Keywords: AKT; Alzheimer’s disease (AD); CXCR4; SH-SY5Y; aging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / genetics
  • Alzheimer Disease / genetics
  • Alzheimer Disease / pathology*
  • Biomarkers / metabolism
  • Cell Line
  • Cell Proliferation / genetics
  • Chemokine CXCL12 / metabolism*
  • Cyclic AMP Response Element-Binding Protein / metabolism*
  • Humans
  • Phosphorylation
  • Protein Transport / physiology
  • Proto-Oncogene Proteins c-akt / metabolism*
  • RNA Interference
  • RNA, Small Interfering / genetics
  • Receptors, CXCR4 / genetics
  • Receptors, CXCR4 / metabolism*
  • Signal Transduction
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • Biomarkers
  • CREB1 protein, human
  • CXCL12 protein, human
  • CXCR4 protein, human
  • Chemokine CXCL12
  • Cyclic AMP Response Element-Binding Protein
  • RNA, Small Interfering
  • Receptors, CXCR4
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Proto-Oncogene Proteins c-akt