Neuroactive Neurosteroids as Endogenous Effectors for the Sigma_1(σ_1)Receptor : Pharmacological Evidence and Therapeutic Opportunities

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概要

• 論文の詳細を見る

• Neuroactive neurosteroids, including progesterone, allopregnanolone, pregnenolone and dehydroepiandrosterone, represent steroid hormones synthesized de novo in the brain and acting locally on nervous cells. Neurosteroids modulate several neurotransmitter systems such as γ-aminobutyric acid type A (GABAA), N-methyl-D-aspartate (NMDA) and acetylcholine receptors. As physiologic consequences, they are involved in neuronal plasticity, learning and memory processes, aggression and epilepsy, and they modulate the responses to stress, anxiety and depression. The σ1-receptor protein was recently purified and its cDNA was cloned in several species. The amino-acid sequences are structurally unrelated to known mammalian proteins, but shared homology with a fungal sterol C8-C7 isomerase. The σ1-receptor ligands exert a potent neuromodulation on excitatory neurotransmitter systems, including the glutamate and cholinergic systems. Consequently, selective σ1 agonists show neuroprotective properties and beneficial effects in memory processes, stress and depression. The evidence of a direct interaction between neurosteroids and σ1 receptors was first suggested by the ability of several steroids to inhibit the binding of σ1-receptor radioligands in vitro and in vivo. A crossed pharmacology between neurosteroids and σ1-receptor ligands was described in several physiological tests and behavioral responses. This review will detail the recent evidence for a common mechanism of action between neurosteroids and σ1-receptor ligands and focus on the potential therapeutic interests of such interaction in the physiopathology of learning and memory impairments, stress, depression and neuroprotection.

• 社団法人 日本薬理学会の論文

著者

• KAMEI Hiroyuki

  Department of Chemical Engineering, Faculty of Engineering, Kansai University

• Kamei H

  Department Of Neuropsychopharmacology And Hospital Pharmacy Nagoya University School Of Medicine

• Kamei Hiroyuki

  Department Of Chemical Engineering Faculty Of Engineering Kansai University

• Phan Van-ly

  Nserm U. 336 Behavioral Neuropharmacology Group Enscm

• Noda Yukihiro

  Department Of Neuropsychopharmacology And Hospital Pharmacy Nagoya University Graduate School Of Med

• Noda Yukihiro

  Department Of Neuropsychopharmacology And Hospital Pharmacy Nagoya University School Of Medicine

• MAURICE Tangui

  INSERM U. 336, Behavioral Neuropharmacology Group, ENSCM

• URANI Alexandre

  NSERM U. 336, Behavioral Neuropharmacology Group, ENSCM

• NABESHIMA Toshitake

  Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University School of Medicine

• Noda Yukihiro

  Department Of Cardiovascular Surgery Fukui Prefectural Hospital

• Maurice Tangui

  Inserm U. 336 Behavioral Neuropharmacology Group Enscm

• Urani Alexandre

  Nserm U. 336 Behavioral Neuropharmacology Group Enscm

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