The Microglial ATP-Gated Ion Channel P2X7 As a CNS Drug Target

被引：174

作者：

Bhattacharya, Anindya ^{[1
]}

Biber, Knut ^{[2
,3
]}

机构：

[1] Janssen Res & Dev, LLC Neurosci Drug Discovery, 3210 Merryfield Row, San Diego, CA USA

[2] Univ Hosp Freiburg, Dept Psychiat & Psychotherapy, Hauptstr 5, Freiburg, Germany

[3] Univ Groningen, Univ Med Ctr Groningen, Dept Neurosci, Ant Deusinglaan 1, Groningen, Netherlands

来源：

GLIA | 2016年 / 64卷 / 10期

关键词：

P2X7; IL-1; beta; microglia; neuroinflammation; depression; mood disorders; pain; neurodegeneration; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; PURINERGIC P2X(7) RECEPTOR; GAIN-OF-FUNCTION; PHARMACOLOGICAL CHARACTERIZATION; AMYLOID-BETA; STATUS EPILEPTICUS; SPINAL-CORD; ALLOSTERIC MODULATORS; RHEUMATOID-ARTHRITIS; ALZHEIMERS-DISEASE;

D O I：

10.1002/glia.23001

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Based on promising preclinical evidence, microglial P2X7 has increasingly being recognized as a target for therapeutic intervention in neurological and psychiatric diseases. However, despite this knowledge no P2X7-related drug has yet entered clinical trials with respect to CNS diseases. We here discuss the current literature on P2X7 being a drug target and identify unsolved issues and still open questions that have hampered the development of P2X7 dependent therapeutic approaches for CNS diseases. It is concluded here that the lack of brain penetrating P2X7 antagonists is a major obstacle in the field and that central P2X7 is a yet untested clinical drug target. In the CNS, microglial P2X7 activation causes neuroinflammation, which in turn plays a role in various CNS disorders. This has resulted in a surge of brain penetrant P2X7 antagonists. P2X7 is a viable, clinically untested CNS drug target.

引用

页码：1772 / 1787

页数：16

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