CX3CL1/CX3CR1 in Alzheimer's Disease: A Target for Neuroprotection

Chen, Peiqing; Zhao, Wenjuan; Guo, Yanjie; Xu, Qin-Juan; Yin, Ming

doi:10.1155/2016/8090918

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CX3CL1/CX3CR1 in Alzheimer's Disease: A Target for Neuroprotection

review-article

Author(s): Peiqing Chen ¹ , Wenjuan Zhao ¹ ^, ^* , Yanjie Guo ² , Juan Xu ¹ , Ming Yin ¹ ^, ^*

Publication date (Electronic): 27 June 2016

Journal: BioMed Research International

Publisher: Hindawi Publishing Corporation

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Abstract

CX3C chemokine ligand 1 (CX3CL1) is an intriguing chemokine belonging to the CX3C family. CX3CL1 is secreted by neurons and plays an important role in modulating glial activation in the central nervous system after binding to its sole receptor CX3CR1 which mainly is expressed on microglia. Emerging data highlights the beneficial potential of CX3CL1-CX3CR1 in the pathogenesis of Alzheimer's disease (AD), a common progressive neurodegenerative disease, and in the progression of which neuroinflammation plays a vital role. Even so, the importance of CX3CL1/CX3CR1 in AD is still controversial and needs further clarification. In this review, we make an attempt to present a concise map of CX3CL1-CX3CR1 associated with AD to find biomarkers for early diagnosis or therapeutic interventions.

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The role of tumor necrosis factor (TNF) as an immune mediator has long been appreciated but its function in the brain is still unclear. TNF receptor 1 (TNFR1) is expressed in most cell types, and can be activated by binding of either soluble TNF (solTNF) or transmembrane TNF (tmTNF), with a preference for solTNF; whereas TNFR2 is expressed primarily by microglia and endothelial cells and is preferentially activated by tmTNF. Elevation of solTNF is a hallmark of acute and chronic neuroinflammation as well as a number of neurodegenerative conditions including ischemic stroke, Alzheimer's (AD), Parkinson's (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). The presence of this potent inflammatory factor at sites of injury implicates it as a mediator of neuronal damage and disease pathogenesis, making TNF an attractive target for therapeutic development to treat acute and chronic neurodegenerative conditions. However, new and old observations from animal models and clinical trials reviewed here suggest solTNF and tmTNF exert different functions under normal and pathological conditions in the CNS. A potential role for TNF in synaptic scaling and hippocampal neurogenesis demonstrated by recent studies suggest additional in-depth mechanistic studies are warranted to delineate the distinct functions of the two TNF ligands in different parts of the brain prior to large-scale development of anti-TNF therapies in the CNS. If inactivation of TNF-dependent inflammation in the brain is warranted by additional pre-clinical studies, selective targeting of TNFR1-mediated signaling while sparing TNFR2 activation may lessen adverse effects of anti-TNF therapies in the CNS.

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Author and article information

Journal

Journal ID (nlm-ta): Biomed Res Int

Journal ID (iso-abbrev): Biomed Res Int

Journal ID (publisher-id): BMRI

Title: BioMed Research International

Publisher: Hindawi Publishing Corporation

ISSN (Print): 2314-6133

ISSN (Electronic): 2314-6141

Publication date (Print): 2016

Publication date (Electronic): 27 June 2016

Volume: 2016

Electronic Location Identifier: 8090918

Affiliations

¹School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China

²Department of Neurology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 100 Haining Road, Shanghai 200080, China

Author notes

*Wenjuan Zhao: zhaowj@ 123456sjtu.edu.cn and

*Ming Yin: myin@ 123456sjtu.edu.cn

Academic Editor: Tauheed Ishrat

Author information

Wenjuan Zhao http://orcid.org/0000-0003-2529-3404

Ming Yin http://orcid.org/0000-0001-6095-1973

Article

DOI: 10.1155/2016/8090918

PMC ID: 4939332

PubMed ID: 27429982

SO-VID: a79a0278-3d4b-4de7-b0dd-da4356fc0908

License:

This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

History

Date received : 18 March 2016

Date accepted : 5 June 2016

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