Year: 2021
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.
Institutions: Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, University of Pittsburgh, Azienda Ospedaliera San Gerardo, University of Milano-Bicocca, University of California, San Francisco, Massachusetts General Hospital, Hofstra University, North Shore University Hospital, Donald & Barbara Zucker School of Medicine at Hofstra/Northwell, Universitat Autònoma de Barcelona, Vall d'Hebron Institut de Recerca, Vall d'Hebron Hospital Universitari, Yale University, University of Maryland, Baltimore
Language: English
Topic: Ion Channels and Receptors
Subfield: Sensory Systems
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,160
OpenAlex ID: W3209536428