Introduction to Sigma Proteins: Evolution of the Concept of Sigma Receptors

  • Felix J. Kim
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 244)


For over 40 years, scientists have endeavored to understand the so-called sigma receptors. During this time, the concept of sigma receptors has continuously and significantly evolved. With thousands of publications on the subject, these proteins have been implicated in various diseases, disorders, and physiological processes. Nevertheless, we are just beginning to understand what sigma proteins do and how they work. Two subtypes have been identified, Sigma1 and Sigma2. Whereas Sigma1 (also known as sigma-1 receptor, Sig1R, σ1 receptor, and several other names) was cloned over 20 years ago, Sigma2 (sigma-2 receptor, σ2 receptor) was cloned very recently and had remained a pharmacologically defined entity. In this volume, we will focus primarily on Sigma1. We will highlight several key subject areas in which Sigma1 has been well characterized as well as (re)emerging areas of interest. Despite the large number of publications regarding Sigma1, several fundamental questions remain unanswered or only partially answered. Most of what we know about Sigma1 comes from pharmacological studies; however, a clearly defined molecular mechanism of action remains elusive. One concept has become clear; Sigma1 is not a traditional receptor. Sigma1 is now considered a unique pharmacologically regulated integral membrane chaperone or scaffolding protein. A number of landmark discoveries over the past decade have begun to reshape the concept of sigma receptors. With the rapid emergence of new information, development of new tools, and changing conceptual frameworks, the field is poised for a period of accelerated progress.


Alcohol abuse Allosteric modulation Anchor patch Cancer Chaperone Crystal structure Drug addiction Drug mechanism of action Imaging agents Medicinal chemistry Neurodegeneration Neuronal excitability Nuclear magnetic resonance Pain Pharmacology Puzzle Scaffold Self-administration Sigma1 Sigma-1 receptor Sigma2 Sigma-2 receptor Small molecule modulator Three-dimensional homology model 


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Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Department of Pharmacology and PhysiologyDrexel University College of MedicinePhiladelphiaUSA
  2. 2.Sidney Kimmel Cancer CenterPhiladelphiaUSA

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