Leveraging the ATP‐P2X7 receptor signalling axis to alleviate traumatic CNS damage and related complications

Author:

Yin Yaling1,Wei Linyu1,Caseley Emily A.2,Lopez‐Charcas Osbaldo3ORCID,Wei Yingjuan1,Li Dongliang14,Muench Steve P.2,Roger Sebastian3,Wang Lu1,Jiang Lin‐Hua12ORCID

Affiliation:

1. Sino‐UK Joint Laboratory of Brain Function and Injury of Henan Province, Department of Physiology and Pathophysiology Xinxiang Medical University Xinxiang China

2. Faculty of Biological Sciences, School of Biomedical Sciences University of Leeds Leeds UK

3. EA4245, Transplantation, Immunology and Inflammation, Faculty of Medicine University of Tours Tours France

4. Sanquan College of Xinxiang Medical University Xinxiang China

Abstract

AbstractThe P2X7 receptor is an exceptional member of the P2X purinergic receptor family, with its activation requiring high concentrations of extracellular adenosine 5ʹ‐triphosphate (ATP) that are often associated with tissue damage and inflammation. In the central nervous system (CNS), it is highly expressed in glial cells, particularly in microglia. In this review, we discuss the role and mechanisms of the P2X7 receptor in mediating neuroinflammation and other pathogenic events in a variety of traumatic CNS damage conditions, which lead to loss of neurological and cognitive functions. We raise the perspective on the steady progress in developing CNS‐penetrant P2X7 receptor‐specific antagonists that leverage the ATP‐P2X7 receptor signaling axis as a potential therapeutic strategy to alleviate traumatic CNS damage and related complications.

Funder

Wellcome Trust

Publisher

Wiley

Subject

Drug Discovery,Pharmacology,Molecular Medicine

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