The Evolution of the Sigma-2 (σ2) Receptor from Obscure Binding Site to Bona Fide Therapeutic Target

Adv Exp Med Biol. 2017;964:49-61. doi: 10.1007/978-3-319-50174-1_5.


The sigma-2 (σ2) receptor represents one of the most poorly understood proteins in cell biology. Although this receptor was identified through in vitro binding studies over 25 years ago, the molecular identity of this protein is currently not unambiguously known, and the results from recent attempts to identify the σ2 receptor through protein purification and mass spectral analysis have been the subject of debate in the literature. However, there is overwhelming data demonstrating that the σ2 receptor is an important biomarker of tumor cell proliferation . The observation that σ2 receptor agonists are potent anticancer agents whereas σ2 antagonists block Aβ1-42 oligomer synaptic dysfunction in transgenic mouse models of Alzheimer's disease have clearly identified this protein as an important therapeutic target for the treatment of a variety of pathological conditions.

Keywords: Agonists; Antagonists; Cancer chemotherapy; Cell proliferation; σ2 receptors.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / metabolism
  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Binding Sites / physiology*
  • Humans
  • Neoplasms / drug therapy
  • Neoplasms / metabolism
  • Receptors, sigma / agonists*
  • Receptors, sigma / antagonists & inhibitors*
  • Receptors, sigma / metabolism


  • Antineoplastic Agents
  • Receptors, sigma
  • sigma-2 receptor