Role of Sigma-1 Receptor in Cocaine Abuse and Neurodegenerative Disease.
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.
Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, 985880 Nebraska Medical Center, DRC 8024, Omaha, NE, 68198-5880, USA.
Yu
Y
Cai
Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, 985880 Nebraska Medical Center, DRC 8024, Omaha, NE, 68198-5880, USA.
Lu
L
Yang
Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, 985880 Nebraska Medical Center, DRC 8024, Omaha, NE, 68198-5880, USA.
Fang
F
Niu
Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, 985880 Nebraska Medical Center, DRC 8024, Omaha, NE, 68198-5880, USA.
Ke
K
Liao
Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, 985880 Nebraska Medical Center, DRC 8024, Omaha, NE, 68198-5880, USA. sbuch@unmc.edu.
Shilpa
S
Buch
D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism; D003042:Cocaine / Q000009:adverse effects; D019970:Cocaine-Related Disorders / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D019636:Neurodegenerative Diseases / Q000378:metabolism*; D017480:Receptors, sigma / Q000378:metabolism*; D000097605:Sigma-1 Receptor
D003042:Cocaine; D008024:Ligands; D017480:Receptors, sigma; D000097605:Sigma-1 Receptor
Alzheimer Disease (AD ); Amyotrophic Lateral Sclerosis (ALS ); Cocaine; Huntington Disease (HD ); Parkinson Disease (PD ); Sigma-1 receptor (Sig-1R)