The Sigma1 Protein as a Target for the Non-genomic Effects of Neuro(active)steroids: Molecular, Physiological, and Behavioral Aspects

• Monnet François P.

  Unité 705 de l’Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche 7157 du Centre National de la Recherche Scientifique, Université de Paris V et VII, Hôpital Lariboisière-Fernand Widal, France

• Maurice Tangui

  Unité 710 de l’Institut National de la Santé et de la Recherche Médicale, Ecole Pratique des Hautes Etudes, Université de Montpellier II, France

書誌事項

タイトル別名

• Sigma1 Protein as a Target for the Non genomic Effects of Neuro active steroids Molecular Physiological and Behavioral Aspects

抄録

Steroids synthesized in the periphery or de novo in the brain, so called ‘neurosteroids’, exert both genomic and nongenomic actions on neurotransmission systems. Through rapid modulatory effects on neurotransmitter receptors, they influence inhibitory and excitatory neurotransmission. In particular, progesterone derivatives like 3α-hydroxy-5α-pregnan-20-one (allopregnanolone) are positive allosteric modulators of the γ-aminobutyric acid type A (GABA_A) receptor and therefore act as inhibitory steroids, while pregnenolone sulphate (PREGS) and dehydroepiandrosterone sulphate (DHEAS) are negative modulators of the GABA_A receptor and positive modulators of the N-methyl-<sc>D</sc>-aspartate (NMDA) receptor, therefore acting as excitatory neurosteroids. Some steroids also interact with atypical proteins, the sigma (σ) receptors. Recent studies particularly demonstrated that the σ₁ receptor contributes effectively to their pharmacological actions. The present article will review the data demonstrating that the σ₁ receptor binds neurosteroids in physiological conditions. The physiological relevance of this interaction will be analyzed and the impact on physiopathological outcomes in memory and drug addiction will be illustrated. We will particularly highlight, first, the importance of the σ₁-receptor activation by PREGS and DHEAS which may contribute to their modulatory effect on calcium homeostasis and, second, the importance of the steroid tonus in the pharmacological development of selective σ₁ drugs.<br>

収録刊行物

• Journal of Pharmacological Sciences

  Journal of Pharmacological Sciences 100 (2), 93-118, 2006

  公益社団法人 日本薬理学会

キーワード

• neuro(active)steroid
• sigma₁ receptor
• neurotransmission
• neuronal plasticity
• learning and memory

詳細情報

• CRID: 1390001205177580928
• NII論文ID: 10018240466
• NII書誌ID: AA11806667
• DOI: 10.1254/jphs.cr0050032
• ISSN: 13478648
• ISSN: 13478613
• NDL書誌ID: 7821806
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I7821806
• Web Site: https://search.jamas.or.jp/link/ui/2006310780
• 本文言語コード: en
• データソース種別:
  • JaLC
  • NDL
  • Crossref
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可