Imaging the Sigma-2 Receptor for Diagnosis and Prediction of Therapeutic Response

Abstract

Sigma (σ) receptors represent a class of proteins that were initially classified as a subtype of the opiate receptors. Subsequent studies revealed that σ binding sites are a distinct class of receptors that are located in the central nervous system as well as in a variety of tissues and organs [1, 2]. Two σ binding site subtypes were distinguished based on differences in their drug-binding profiles and molecular weight. The two binding sites are known as σ1 and σ2 receptors. σ1 receptors have a molecular weight of ~25 kDa, whereas σ2 receptors have a molecular weight of ~21.5 kDa [3]. The σ1 receptor has been cloned and displays a 30% sequence homology with the enzyme, yeast C8-C7 sterol isomerase [4, 5], but this receptor lacks C8-C7 isomerase activity. Recent studies have shown that neuroactive steroids bind with moderate affinity to σ1 sites, and suggest that σ1 receptors may modulate the activity of GABA and NMDA receptors in the CNS [6-8]. The σ2 receptor has not been cloned, and most of what is known regarding the σ2 receptor has been obtained through the use of in vitro receptor binding studies aimed at the pharmacological characterization of this receptor.