Role of Sigma-1 Receptor in Cocaine Abuse and Neurodegenerative Disease.

Abstract

Sigma-1 receptors (Sig-1R) are recognized as a unique class of non-G protein-coupled intracellular protein. Sig-1R binds to its ligand such as cocaine , resulting in dissociation of Sig-1R from mitochondrion-associated ER membrane (MAM) to the endoplasmic reticulum (ER), plasma membrane, and nuclear membrane, regulating function of various proteins. Sig-1R has diverse roles in both physiological as well as in pathogenic processes. The disruption of Sig-1R pathways has been implicated as causative mechanism(s) in the development of both neurodegenerative disorders such as Alzheimer disease (AD ), Parkinson disease (PD ), amyotrophic lateral sclerosis (ALS ) and Huntington Disease (HD ) . Additionally, the interaction of cocaine and Sig-1R has more recently been implicated in potentiating the pathogenesis of HIV-associated neurocognitive disorders (HAND) through impairment of blood-brain barrier (BBB), microglial activation and astrogliosis. On the other hand, restoration of Sig-1R homeostasis has been shown to exert neuroprotective effects. In this review, we provide an overview of how Sig-1R plays a role in the pathogenesis of neurodegenerative disorders and cocaine and implications for future development of therapeutic strategies.

• Authors: Yu Cai, Lu Yang, Fang Niu, Ke Liao, Shilpa Buch
• Journal: Advances in experimental medicine and biology (Adv Exp Med Biol) Vol. 964 Pg. 163-175 ( 2017) ISSN: 0065-2598 [Print] United States
• PMID: 28315271 (Publication Type: Journal Article, Review)

Chemical References

• Ligands
• Receptors, sigma
• Cocaine

Topics

• Animals
• Blood-Brain Barrier (metabolism)
• Cocaine (adverse effects)
• Cocaine-Related Disorders (metabolism)
• Humans
• Ligands
• Neurodegenerative Diseases (metabolism)
• Receptors, sigma (metabolism)
• Sigma-1 Receptor