title: Role of sigma-1 receptors in neurodegenerative diseases.
abstract: Neurodegenerative diseases with distinct genetic etiologies and pathological phenotypes appear to share common mechanisms of neuronal cellular dysfunction, including excitotoxicity, calcium dysregulation, oxidative damage, ER stress and mitochondrial dysfunction. Glial cells, including microglia and astrocytes, play an increasingly recognized role in both the promotion and prevention of neurodegeneration. Sigma receptors, particularly the sigma-1 receptor subtype, which are expressed in both neurons and glia of multiple regions within the central nervous system, are a unique class of intracellular proteins that can modulate many biological mechanisms associated with neurodegeneration. These receptors therefore represent compelling putative targets for pharmacologically treating neurodegenerative disorders. In this review, we provide an overview of the biological mechanisms frequently associated with neurodegeneration, and discuss how sigma-1 receptors may alter these mechanisms to preserve or restore neuronal function. In addition, we speculate on their therapeutic potential in the treatment of various neurodegenerative disorders.
authors.affiliation: Department of Basic Pharmaceutical Sciences, West Virginia University, School of Pharmacy, One Medical Center Drive, Morgantown, WV 26506, United States; Department of Behavioral Medicine and Psychiatry, West Virginia University, School of Medicine, One Medical Center Drive, Morgantown, WV 26506, United States; Department of Physiology and Pharmacology, West Virginia University, School of Medicine, One Medical Center Drive, Morgantown, WV 26506, United States.
authors.forename: Linda
authors.initials: L
authors.lastname: Nguyen
authors.affiliation: Graduate Program in Neuroscience, West Virginia University, School of Medicine, One Medical Center Drive, Morgantown, WV 26506, United States.
authors.forename: Brandon P
authors.initials: BP
authors.lastname: Lucke-Wold
authors.affiliation: Department of Biological and Pharmaceutical Sciences, Touro University California, College of Pharmacy, 1310 Club Drive, Vallejo, CA 94592, United States.
authors.forename: Shona A
authors.initials: SA
authors.lastname: Mookerjee
authors.affiliation: Graduate Program in Neuroscience, West Virginia University, School of Medicine, One Medical Center Drive, Morgantown, WV 26506, United States.
authors.forename: John Z
authors.initials: JZ
authors.lastname: Cavendish
authors.affiliation: Department of Pharmacology, Vanderbilt University School of Medicine, 465 21st Ave, Nashville, TN 37232, United States.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Robson
authors.affiliation: Department of Basic Pharmaceutical Sciences, West Virginia University, School of Pharmacy, One Medical Center Drive, Morgantown, WV 26506, United States; Department of Behavioral Medicine and Psychiatry, West Virginia University, School of Medicine, One Medical Center Drive, Morgantown, WV 26506, United States; Department of Physiology and Pharmacology, West Virginia University, School of Medicine, One Medical Center Drive, Morgantown, WV 26506, United States.
authors.forename: Anna L
authors.initials: AL
authors.lastname: Scandinaro
authors.affiliation: Department of Basic Pharmaceutical Sciences, West Virginia University, School of Pharmacy, One Medical Center Drive, Morgantown, WV 26506, United States; Department of Behavioral Medicine and Psychiatry, West Virginia University, School of Medicine, One Medical Center Drive, Morgantown, WV 26506, United States; Department of Physiology and Pharmacology, West Virginia University, School of Medicine, One Medical Center Drive, Morgantown, WV 26506, United States; Department of Biological and Pharmaceutical Sciences, Touro University California, College of Pharmacy, 1310 Club Drive, Vallejo, CA 94592, United States. Electronic address: rae.matsumoto@tu.edu.
authors.forename: Rae R
authors.initials: RR
authors.lastname: Matsumoto
mesh_terms: D000818:Animals; D006801:Humans; D008954:Models, Biological; D058990:Molecular Targeted Therapy / Q000379:methods; D009410:Nerve Degeneration / Q000503:physiopathology*; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000503:physiopathology*; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D017480:Receptors, sigma / Q000819:agonists / Q000502:physiology*; D000097605:Sigma-1 Receptor
chemical_list: D018696:Neuroprotective Agents; D017480:Receptors, sigma; D000097605:Sigma-1 Receptor
keywords: Neurodegeneration; Neuroprotection; Neurotoxicity; Reactive gliosis; Sigma-1 receptors