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An update on the development of drugs for neuropsychiatric disorders: focusing on the σ1 receptor ligand

An update on the development of drugs for neuropsychiatric disorders: focusing on the σ1 receptor... The σ1 receptor is an intracellular molecule that shares no homology with any mammalian proteins. σ1 receptors normally localize at the endoplasmic reticulum and regulate a variety of signal transductions including intracellular Ca2+ dynamics and neurotrophic factor signaling. In the brain, σ1 receptors are known to regulate the activity of diverse ion channels via protein–protein interactions. Accumulated evidences strongly indicate that the activation/upregulation of σ1 receptors promotes the neuronal differentiation as well as a robust antiapoptotic action. In animals, σ1 receptor agonists exhibit an antidepressant-like action. Furthermore, the agonists enhanced neuronal survival eventhough they were administered several hours after a brain ischemia. Thus, primary clinical targets of σ1 receptor ligands are proposed to include stroke, neurodegenerative disorders and depression. Ligands for the σ1 receptor may constitute a new class of therapeutic drugs targeting an endoplasmic reticular protein. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Expert Opinion on Therapeutic Targets Taylor & Francis

An update on the development of drugs for neuropsychiatric disorders: focusing on the σ1 receptor ligand

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References (114)

Publisher
Taylor & Francis
Copyright
© Informa UK Ltd
ISSN
1744-7631
eISSN
1472-8222
DOI
10.1517/14728222.12.1.45
Publisher site
See Article on Publisher Site

Abstract

The σ1 receptor is an intracellular molecule that shares no homology with any mammalian proteins. σ1 receptors normally localize at the endoplasmic reticulum and regulate a variety of signal transductions including intracellular Ca2+ dynamics and neurotrophic factor signaling. In the brain, σ1 receptors are known to regulate the activity of diverse ion channels via protein–protein interactions. Accumulated evidences strongly indicate that the activation/upregulation of σ1 receptors promotes the neuronal differentiation as well as a robust antiapoptotic action. In animals, σ1 receptor agonists exhibit an antidepressant-like action. Furthermore, the agonists enhanced neuronal survival eventhough they were administered several hours after a brain ischemia. Thus, primary clinical targets of σ1 receptor ligands are proposed to include stroke, neurodegenerative disorders and depression. Ligands for the σ1 receptor may constitute a new class of therapeutic drugs targeting an endoplasmic reticular protein.

Journal

Expert Opinion on Therapeutic TargetsTaylor & Francis

Published: Jan 1, 2008

Keywords: Alzheimer's disease; antidepressant; antipsychotic; depression; endoplasmic reticulum; neurodegenerative disorder; neurotrophic factor, σ; receptor; σ 1 receptor; stroke

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