Neuroactive neurosteroids as endogenous effecters for the sigma11) receptor: Pharmacological evidence and therapeutic opportunities

Tangui Maurice, Vân Ly Phan, Alexandre Urani, Hiroyuki Kamei, Yukihiro Noda, Toshitaka Nabeshima

研究成果: Review article査読

189 被引用数 (Scopus)

抄録

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 (GABA(A)), 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.

本文言語English
ページ(範囲)125-155
ページ数31
ジャーナルJapanese Journal of Pharmacology
81
2
DOI
出版ステータスPublished - 1999

All Science Journal Classification (ASJC) codes

  • 薬理学

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