Sulfonylurea Receptor 1 in Central Nervous System Injury: An Updated Review

Ruchira M. Jha, Department of Neurology, Barrow Neurological Institute and St. Joseph's Hospital and Medical Center, Phoenix, AZ 85013, USA.Follow
Anupama Rani, Department of Translational Neuroscience, Barrow Neurological Institute and St. Joseph's Hospital and Medical Center, Phoenix, AZ 85013, USA.
Shashvat M. Desai, Department of Neurology, Barrow Neurological Institute and St. Joseph's Hospital and Medical Center, Phoenix, AZ 85013, USA.
Sudhanshu Raikwar, Department of Translational Neuroscience, Barrow Neurological Institute and St. Joseph's Hospital and Medical Center, Phoenix, AZ 85013, USA.
Sandra Mihaljevic, Department of Translational Neuroscience, Barrow Neurological Institute and St. Joseph's Hospital and Medical Center, Phoenix, AZ 85013, USA.
Amanda Munoz-Casabella, Department of Translational Neuroscience, Barrow Neurological Institute and St. Joseph's Hospital and Medical Center, Phoenix, AZ 85013, USA.
Patrick M. Kochanek, Clinical and Translational Science Institute, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Joshua Catapano, Department of Neurosurgery, Barrow Neurological Institute and St. Joseph's Hospital and Medical Center, Phoenix, AZ 85013, USA.Follow
Ethan Winkler, Department of Neurosurgery, Barrow Neurological Institute and St. Joseph's Hospital and Medical Center, Phoenix, AZ 85013, USA.
Giuseppe Citerio, School of Medicine and Surgery, University of Milan-Bicocca, 20126 Milan, Italy.
J Claude Hemphill, Department of Neurology, University of California, San Francisco, CA 94143, USA.
W Taylor Kimberly, Division of Neurocritical Care and Center for Genomic Medicine, Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA.
Raj Narayan, Department of Neurosurgery, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, North Shore University Hospital, Manhasset, NY 11549, USA.
Juan Sahuquillo, Neurotrauma and Neurosurgery Research Unit (UNINN), Vall d'Hebron Research Institute (VHIR), 08035 Barcelona, Spain.
Kevin N. Sheth, Division of Neurocritical Care and Emergency Neurology, Department of Neurology, School of Medicine, Yale University, New Haven, CT 06510, USA.
J Marc Simard, Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA.

Document Type

Article

Abstract

Sulfonylurea receptor 1 (SUR1) is a member of the adenosine triphosphate (ATP)-binding cassette (ABC) protein superfamily, encoded by Abcc8, and is recognized as a key mediator of central nervous system (CNS) cellular swelling via the transient receptor potential melastatin 4 (TRPM4) channel. Discovered approximately 20 years ago, this channel is normally absent in the CNS but is transcriptionally upregulated after CNS injury. A comprehensive review on the pathophysiology and role of SUR1 in the CNS was published in 2012. Since then, the breadth and depth of understanding of the involvement of this channel in secondary injury has undergone exponential growth: SUR1-TRPM4 inhibition has been shown to decrease cerebral edema and hemorrhage progression in multiple preclinical models as well as in early clinical studies across a range of CNS diseases including ischemic stroke, traumatic brain injury, cardiac arrest, subarachnoid hemorrhage, spinal cord injury, intracerebral hemorrhage, multiple sclerosis, encephalitis, neuromalignancies, pain, liver failure, status epilepticus, retinopathies and HIV-associated neurocognitive disorder. Given these substantial developments, combined with the timeliness of ongoing clinical trials of SUR1 inhibition, now, another decade later, we review advances pertaining to SUR1-TRPM4 pathobiology in this spectrum of CNS disease-providing an overview of the journey from patch-clamp experiments to phase III trials.

Keywords

SUR 1, TRPM4, cellular swelling, clinical trials, edema, stroke, sulfonylurea receptor, traumatic brain injury

Medical Subject Headings

Animals; Brain Injuries (etiology, metabolism, pathology); Central Nervous System Diseases (etiology, metabolism, pathology); Humans; Sulfonylurea Receptors (metabolism)

Publication Date

11-2-2021

Publication Title

International journal of molecular sciences

E-ISSN

1422-0067

Volume

22

Issue

21

PubMed ID

34769328

Digital Object Identifier (DOI)

10.3390/ijms222111899

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