Role of sigma-1 receptor in cocaine abuse and neurodegenerative disease

Yu Cai, Lu Yang, Fang Niu, Ke Liao, Shilpa Buch

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)163-175
Number of pages13
JournalAdvances in experimental medicine and biology
StatePublished - 2017


  • Alzheimer disease (AD)
  • Amyotrophic lateral sclerosis (ALS)
  • Cocaine
  • Huntington disease (HD)
  • Parkinson disease (PD)
  • Sigma-1 receptor (Sig-1R)

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology


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