title: Sigma receptors as potential therapeutic targets for neuroprotection.
abstract: Sigma receptors comprise a unique family of proteins that have been implicated in the pathophysiology and treatment of many central nervous system disorders, consistent with their high level of expression in the brain and spinal cord. Mounting evidence indicate that targeting sigma receptors may be particularly beneficial in a number of neurodegenerative conditions including Alzheimer׳s disease, Parkinson׳s disease, stroke, methamphetamine neurotoxicity, Huntington׳s disease, amyotrophic lateral sclerosis, and retinal degeneration. In this perspective, a brief overview is given on sigma receptors, followed by a focus on common mechanisms of neurodegeneration that appear amenable to modulation by sigma receptor ligands to convey neuroprotective effects and/or restorative functions. Within each of the major mechanisms discussed herein, the neuroprotective effects of sigma ligands are summarized, and when known, the specific sigma receptor subtype(s) involved are identified. Together, the literature suggests sigma receptors may provide a novel target for combatting neurodegenerative diseases through both neuronal and glial mechanisms.
authors.affiliation: Graduate Program in Pharmaceutical and Pharmacological Sciences, West Virginia University, Morgantown, WV 26506, USA.
authors.forename: Linda
authors.initials: L
authors.lastname: Nguyen
authors.affiliation: Graduate Program in Pharmaceutical and Pharmacological Sciences, West Virginia University, Morgantown, WV 26506, USA.
authors.forename: Nidhi
authors.initials: N
authors.lastname: Kaushal
authors.affiliation: Graduate Program in Pharmaceutical and Pharmacological Sciences, West Virginia University, Morgantown, WV 26506, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Robson
authors.affiliation: Graduate Program in Pharmaceutical and Pharmacological Sciences, West Virginia University, Morgantown, WV 26506, USA. Electronic address: rae.matsumoto@tu.edu.
authors.forename: Rae R
authors.initials: RR
authors.lastname: Matsumoto
mesh_terms: D000818:Animals; D006801:Humans; D008024:Ligands; D019636:Neurodegenerative Diseases / Q000188:drug therapy*; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D017480:Receptors, sigma / Q000378:metabolism*
chemical_list: D008024:Ligands; D018696:Neuroprotective Agents; D017480:Receptors, sigma
keywords: Glia; Neurodegeneration; Neurotoxicity; Sigma receptors