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Adv Protein Chem Struct Biol. 2016;103:137-67. doi: 10.1016/bs.apcsb.2015.10.002. Epub 2015 Nov 21.

Acid-Sensing Ion Channels as Potential Pharmacological Targets in Peripheral and Central Nervous System Diseases.

Author information

1
Department of Neurological and Movement Sciences, Section of Anatomy and Histology, University of Verona, Verona, Italy; Department of Anatomy, Animal Physiology and Biophysics, Faculty of Biology, University of Bucharest, Bucharest, Romania.
2
Department of Anatomy, Animal Physiology and Biophysics, Faculty of Biology, University of Bucharest, Bucharest, Romania.
3
Department of Neurological and Movement Sciences, Section of Anatomy and Histology, University of Verona, Verona, Italy; Department of Life and Environmental Physics, 'Horia Hulubei' National Institute for Physics and Nuclear Engineering, Magurele, Romania. Electronic address: mihai.radu@univr.it.

Abstract

Acid-sensing ion channels (ASICs) are widely expressed in the body and represent good sensors for detecting protons. The pH drop in the nervous system is equivalent to ischemia and acidosis, and ASICs are very good detectors in discriminating slight changes in acidity. ASICs are important pharmacological targets being involved in a variety of pathophysiological processes affecting both the peripheral nervous system (e.g., peripheral pain, diabetic neuropathy) and the central nervous system (e.g., stroke, epilepsy, migraine, anxiety, fear, depression, neurodegenerative diseases, etc.). This review discusses the role played by ASICs in different pathologies and the pharmacological agents acting on ASICs that might represent promising drugs. As the majority of above-mentioned pathologies involve not only neuronal dysfunctions but also microvascular alterations, in the next future, ASICs may be also considered as potential pharmacological targets at the vasculature level. Perspectives and limitations in the use of ASICs antagonists and modulators as pharmaceutical agents are also discussed.

KEYWORDS:

Acid-sensing ion channels; Epilepsy; Migraine; Neurodegenerative disorders; Peripheral pain; Pharmacology; Protein–protein coupling; Psychiatric disorders; Stroke

PMID:
26920689
DOI:
10.1016/bs.apcsb.2015.10.002
[Indexed for MEDLINE]

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