Sigma-1 receptor as regulator of neuronal intracellular Ca super(2+): clinical and therapeutic relevance

Preserving brain function and cognitive faculties during aging and psychiatric diseases (e.g. psychotic, anxiety and affective disorders, dementia) is essential for the self-reliance and quality of life of patients. Cognitive loss involves not only memory, but also motor function. The decrease of ca...

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Bibliographic Details
Published in:Biology of the cell 2005-12, Vol.97 (12), p.873-883
Main Author: Monnet, F P
Format: Article
Language:English
Online Access:Get full text
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Summary:Preserving brain function and cognitive faculties during aging and psychiatric diseases (e.g. psychotic, anxiety and affective disorders, dementia) is essential for the self-reliance and quality of life of patients. Cognitive loss involves not only memory, but also motor function. The decrease of catecholaminergic and excitatory neurotransmissions, as well as of protein phosphorylation, have currently been identified as prominent biological markers of the abovementioned diseases. Such deleterious biological events are well known to occur downstream of a progressive decline of intracellular Ca super(2+) signalling. This latter constitutes a key target for the neuronal plasticity that has also been reported during aging and psychiatric disorders. Most of the medicines used in psychiatry are active on the sigma-1 receptor. This membrane bound receptor is widely distributed in memory-associated cortical and motor-related brainstem areas, prompting the hypothesis that it might contribute to the pathophysiology of these behavioural brain diseases. The sigma-1 receptor is characterized by a unique mode of action by regulating both Ca super(2+) entry at the plasma membrane level (i.e. via potassium channels, voltage-sensitive Ca super(2+) channels) and Ca super(2+) mobilization from endoplasmic stores [i.e. via Ins(1,4,5)P sub(3) receptors]. This review presents recent data supporting the notion that drugs acting via the endoplasmic reticulum-coupled sigma-1 receptor might reverse these deleterious events by restoring both extra- and intra-cellular Ca super(2+)-dependent neuronal responses.
ISSN:0248-4900
DOI:10.1042/BC20040149