Neurosteroids, like allopregnanolone and pregnanolone, are endogenous regulators of neuronal excitability. Inside the brain, they are highly selective and potent modulators of GABAA receptor activity. Their anticonvul...Neurosteroids, like allopregnanolone and pregnanolone, are endogenous regulators of neuronal excitability. Inside the brain, they are highly selective and potent modulators of GABAA receptor activity. Their anticonvulsant, anesthetics and anxiolytic properties are useful for the treatments of several neurological and psychiatric disorders via reducing the risks of side effects obtained with the commercial drugs. The principal disadvantages of endogenous neurosteroids adminis- tration are their rapid metabolism and their low oral bioavailability. Synthetic steroids analogues with major stability or endogenous neurosteroids stimulation synthesis might constitute prom- ising novel strategies for the treatment of several disorders. Numerous studies indicate that the 3ct-hydroxyl configuration is the key for binding and activity, but modifications in the steroid nucleus may emphasize different pharmacophores. So far, several synthetic steroids have been developed with successful neurosteroid-like effects. In this work, we summarize the properties of various synthetic steroids probed in trials throughout the analysis of several neurosteroids-like actions.展开更多
A new role has emerged for progesterone after discovering its potent actions away from reproduction in both the central and the peripheral nervous system. The aim of the present report is to discuss progesterone’s me...A new role has emerged for progesterone after discovering its potent actions away from reproduction in both the central and the peripheral nervous system. The aim of the present report is to discuss progesterone’s mechanisms of action involved in myelination, remyelination and neuroinflammation. The pivotal role of the classic progesterone receptor is described and evidence is compiled about progesterone’s direct effects on oligodendrocyte linage and its indirect effects on oligodendrocyte precursor cell differentiation by decreasing the neuroinflammatory environment.展开更多
Central nervous system(CNS)injuries and neurodegenerative diseases show a broad spectrum of common pathophysiological processes,including oxidative stress,neuroinflammation,excitotoxicity,demyelination and neurotransm...Central nervous system(CNS)injuries and neurodegenerative diseases show a broad spectrum of common pathophysiological processes,including oxidative stress,neuroinflammation,excitotoxicity,demyelination and neurotransmission dysfunctions.Over the past decades,valuable experimental investigations have helped to clarify the role and timing of these multiple molecular and cellular mechanisms in each of these particular disorders,which usually overlap and critically contribute to long-term disability.However,up to now,no definite cures or effective disease-modifying therapies are available for any of these conditions.This has led to an active search of novel therapeutic approaches,including the repositioning of existing drugs for new indications,as a valid approach to promptly move candidate molecules to clinical trials.展开更多
基金supported by grants from Agencia Nacional de Promocion Cientifica y Tecnologica(ANPCYT,PICT-2006-727)Consejo Nacional de Investigaciones Científicas y Técnicas(CONICET,PIP-860)
文摘Neurosteroids, like allopregnanolone and pregnanolone, are endogenous regulators of neuronal excitability. Inside the brain, they are highly selective and potent modulators of GABAA receptor activity. Their anticonvulsant, anesthetics and anxiolytic properties are useful for the treatments of several neurological and psychiatric disorders via reducing the risks of side effects obtained with the commercial drugs. The principal disadvantages of endogenous neurosteroids adminis- tration are their rapid metabolism and their low oral bioavailability. Synthetic steroids analogues with major stability or endogenous neurosteroids stimulation synthesis might constitute prom- ising novel strategies for the treatment of several disorders. Numerous studies indicate that the 3ct-hydroxyl configuration is the key for binding and activity, but modifications in the steroid nucleus may emphasize different pharmacophores. So far, several synthetic steroids have been developed with successful neurosteroid-like effects. In this work, we summarize the properties of various synthetic steroids probed in trials throughout the analysis of several neurosteroids-like actions.
文摘A new role has emerged for progesterone after discovering its potent actions away from reproduction in both the central and the peripheral nervous system. The aim of the present report is to discuss progesterone’s mechanisms of action involved in myelination, remyelination and neuroinflammation. The pivotal role of the classic progesterone receptor is described and evidence is compiled about progesterone’s direct effects on oligodendrocyte linage and its indirect effects on oligodendrocyte precursor cell differentiation by decreasing the neuroinflammatory environment.
基金supported by grants from Consejo Nacional de Investigaciones Científicas y Tecnológicas(CONICET,PIP 112-201501-00266)Agencia Nacional de Promoción Científica y Técnica(PICT 2018-02152)Fundación RenéBarón and Fundación Williams
文摘Central nervous system(CNS)injuries and neurodegenerative diseases show a broad spectrum of common pathophysiological processes,including oxidative stress,neuroinflammation,excitotoxicity,demyelination and neurotransmission dysfunctions.Over the past decades,valuable experimental investigations have helped to clarify the role and timing of these multiple molecular and cellular mechanisms in each of these particular disorders,which usually overlap and critically contribute to long-term disability.However,up to now,no definite cures or effective disease-modifying therapies are available for any of these conditions.This has led to an active search of novel therapeutic approaches,including the repositioning of existing drugs for new indications,as a valid approach to promptly move candidate molecules to clinical trials.
