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

• Published in: International journal of molecular sciences 2021-11, Vol.22 (21), p.11899
• Main Authors: Jha, Ruchira M, Rani, Anupama, Desai, Shashvat M, Raikwar, Sudhanshu, Mihaljevic, Sandra, Munoz-Casabella, Amanda, Kochanek, Patrick M, Catapano, Joshua, Winkler, Ethan, Citerio, Giuseppe, Hemphill, J Claude, Kimberly, W Taylor, Narayan, Raj, Sahuquillo, Juan, Sheth, Kevin N, Simard, J Marc
• Format: Article
• Language: English
• Subjects: ABC transporters; Adenosine triphosphate; Animals; Apoptosis; ATP; Binding sites; Brain Injuries - etiology; Brain Injuries - metabolism; Brain Injuries - pathology; cellular swelling; Central nervous system; Central Nervous System Diseases - etiology; Central Nervous System Diseases - metabolism; Central Nervous System Diseases - pathology; Clinical trials; Cognition; Cytotoxicity; Edema; Encephalitis; Epilepsy; Experiments; Hemorrhage; Humans; Ischemia; Liver diseases; Multiple sclerosis; Nervous system; Potassium; Proteins; Review; Reviews; stroke; Subarachnoid hemorrhage; Sulfonylurea; sulfonylurea receptor; Sulfonylurea Receptors - metabolism; SUR 1; Transcription; Transient receptor potential proteins; Traumatic brain injury
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms222111899

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.