title: Sigma-1 receptor chaperones in neurodegenerative and psychiatric disorders.
abstract: BACKGROUND
  Sigma-1 receptors (Sig-1Rs) are molecular chaperones that reside mainly in the endoplasmic reticulum (ER) but exist also in the proximity of the plasma membrane. Sig-1Rs are highly expressed in the CNS and are involved in many cellular processes including cell differentiation, neuritogenesis, microglia activation, protein quality control, calcium-mediated ER stress and ion channel modulation. Disturbance in any of the above cellular processes can accelerate the progression of many neurological disorders; therefore, the Sig-1R has been implicated in several neurological diseases.
  
  
  METHODS
  This review broadly covers the functions of Sig-1Rs including several neurodegenerative disorders in humans and drug addiction-associated neurological disturbance in the case of HIV infection. We discuss how several Sig-1R ligands could be utilized in therapeutic approaches to treat those disorders.
  
  
  CONCLUSIONS
  Emerging understanding of the cellular functions of this unique transmembrane chaperone may lead to the use of new agents or broaden the use of certain available ligands as therapeutic targets in those neurological disorders.
authors.affiliation: National Institute on Drug Abuse, National Institutes of Health, Cellular Pathobiology Section, Integral Neuroscience Branch , Baltimore, MD 21224 , USA stsai@intra.nida.nih.gov ; tsu@intra.nida.nih.gov.
authors.forename: Shang-Yi A
authors.initials: SY
authors.lastname: Tsai
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Pokrass
authors.forename: Neal R
authors.initials: NR
authors.lastname: Klauer
authors.forename: Nicole E
authors.initials: NE
authors.lastname: De Credico
authors.forename: Tsung-Ping
authors.initials: TP
authors.lastname: Su
mesh_terms: D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D001523:Mental Disorders / Q000188:drug therapy / Q000378:metabolism*; D018832:Molecular Chaperones / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D009292:Narcotic Antagonists / Q000008:administration & dosage; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000378:metabolism*; D017480:Receptors, sigma / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D000097605:Sigma-1 Receptor
chemical_list: D018832:Molecular Chaperones; D009292:Narcotic Antagonists; D017480:Receptors, sigma; D000097605:Sigma-1 Receptor
keywords: Alzheimer’s disease; HIV-associated neurodementia; Parkinson’s disease; amyotrophic lateral sclerosis; frontotemporal lobar degeneration; neurodegenerative diseases; psychiatric disorders; sigma-1 receptor