H Li1, L Hao, Y Li, R Wang. 1. Rong Wang, Central Laboratory, Department of General Surgery, Center of Alzheimer's Disease, Beijing Institute for Brain Disorders, Key Laboratory for Neurodegenerative Disease of Ministry of Education, Xuan Wu Hospital, Capital Medical University, Beijing, China, rong_wang72@aliyun.com.
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.
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.
Authors: T Sasaki; J Irie-Sasaki; R G Jones; A J Oliveira-dos-Santos; W L Stanford; B Bolon; A Wakeham; A Itie; D Bouchard; I Kozieradzki; N Joza; T W Mak; P S Ohashi; A Suzuki; J M Penninger Journal: Science Date: 2000-02-11 Impact factor: 47.728
Authors: Nassim Dali-Youcef; Marie Lagouge; Sébastien Froelich; Christian Koehl; Kristina Schoonjans; Johan Auwerx Journal: Ann Med Date: 2007 Impact factor: 4.709
Authors: E Hirsch; V L Katanaev; C Garlanda; O Azzolino; L Pirola; L Silengo; S Sozzani; A Mantovani; F Altruda; M P Wymann Journal: Science Date: 2000-02-11 Impact factor: 47.728
Authors: C Limatola; A Giovannelli; L Maggi; D Ragozzino; L Castellani; M T Ciotti; F Vacca; D Mercanti; A Santoni; F Eusebi Journal: Eur J Neurosci Date: 2000-07 Impact factor: 3.386