Genomic Action of Sigma-1 Receptor Chaperone Relates to Neuropathic Pain.

Sigma-1 receptors (Sig-1Rs) are endoplasmic reticulum (ER) chaperones implicated in neuropathic pain. Here we examine if the Sig-1R may relate to neuropathic pain at the level of dorsal root ganglia (DRG). We focus on the neuronal excitability of DRG in a "spare nerve injury" (SNI) model of neuropathic pain in rats and find that Sig-1Rs likely contribute to the genesis of DRG neuronal excitability by decreasing the protein level of voltage-gated Cav2.

Knocking Out Sigma-1 Receptors Reveals Diverse Health Problems.

Sigma-1 receptor (Sig-1R) is a protein present in several organs such as brain, lung, and heart. In a cell, Sig-1R is mainly located across the membranes of the endoplasmic reticulum and more specifically at the mitochondria-associated membranes. Despite numerous studies showing that Sig-1R could be targeted to rescue several cellular mechanisms in different pathological conditions, less is known about its fundamental relevance.

Sigma-1 Receptor Agonists Induce Oxidative Stress in Mitochondria and Enhance Complex I Activity in Physiological Condition but Protect Against Pathological Oxidative Stress.

The sigma receptor (σR) is a chaperone protein residing at mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs), where it modulates Ca exchange between the ER and mitochondria by interacting with inositol-1,4,5 trisphosphate receptors (IPRs). The σR is highly expressed in the central nervous system and its activation stimulates neuromodulation and neuroprotection, for instance in Alzheimer's disease (AD) models in vitro and in vivo. σR effects on mitochondria pathophysiology and the downstream signaling are still not fully understood.

Role of σ Receptors in Learning and Memory and Alzheimer's Disease-Type Dementia.

The present chapter will review the role of σ receptor in learning and memory and neuroprotection , against Alzheimer's type dementia. σ Receptor agonists have been tested in a variety of pharmacological and pathological models of learning impairments in rodents these last past 20 years. Their anti-amnesic effects have been explained by the wide-range modulatory role of σ receptors on Ca mobilizations, neurotransmitter responses, and particularly glutamate and acetylcholine systems, and neurotrophic factors.

Sigma-1 (σ) Receptor in Memory and Neurodegenerative Diseases.

The sigma-1 (σ) receptor has been associated with regulation of intracellular Ca homeostasis, several cellular signaling pathways, and inter-organelle communication, in part through its chaperone activity. In vivo, agonists of the σ receptor enhance brain plasticity, with particularly well-described impact on learning and memory. Under pathological conditions, σ receptor agonists can induce cytoprotective responses.

Sigma-1 receptor directly interacts with Rac1-GTPase in the brain mitochondria.

Background: Small Rho-GTPases are critical mediators of neuronal plasticity and are involved in the pathogenesis of several psychiatric and neurological disorders. Rac-GTPase forms a multiprotein complex with upstream and downstream regulators that are essential for the spatiotemporal transmission of Rac signaling. The sigma-1 receptor (Sig1R) is a ligand-regulated membrane protein chaperone, and multiprotein complex assembly is essential to sigma-receptor function.