About Sigma Receptors
Sigma receptors are a unique family of proteins, present mainly in the central nervous system (CNS) but also in various peripheral tissues. The receptors are classified into two subtypes: the sigma-1 and sigma-2. These subtypes are distinguishable pharmacologically, functionally and by molecular size. Sigma-1 receptors have been cloned and shown to be distinct from any known receptor class.
Both sigma receptor subtypes are highly expressed in tumor cell lines from various tissues. These include neuroblastomas, glioma, melanoma and carcinoma cell lines of breast, prostate and lung. Interestingly, sigma receptors are more highly expressed in rapidly proliferating cells and are down-regulated when cells become inactive. Their high density in various tumor cell types, and particularly in proliferating cells, makes sigma receptors a potential target for diagnostic imaging as well as therapeutic agents. Recent data suggests that sigma-2 receptor agonists induce cell death in various tumor cell lines including prostate and breast carcinoma, with features consistent with apoptosis. Sigma-2 receptor agonists are reported to induce apoptosis by a novel mechanism, exhibiting similar potency in tumors with wild-type or mutant p53 gene, unlike other agents such as DNA-damaging agents. The mechanism of sigma-2 receptor-mediated apoptosis differs from that of agents that trigger DNA damage, based on observations with inhibitors of caspases. The involvement of distinct apoptotic pathways is further supported by the ability of sigma agonists to potentiate the cytotoxicity of DNA-damaging antineoplastics in various tumor cell lines.
About Anavex Life Sciences Corp.
|SOURCE Anavex Life Sciences Corp.|
Copyright©2008 PR Newswire.
All rights reserved