Sigma-1 receptors (S1Rs) are chaperone proteins usually located on the mitochondria-associated membrane (MAM) of the endoplasmic reticulum (ER) and are thought to play a neuroprotective role by modulating ER stress proteins to promote cell survival. In cases of high ER stress or high concentration of agonists, S1Rs translocate from the MAM ER to the plasma membrane (PM). The roles of S1Rs have been studied in mice and other animal models, but they have yet to be well-evaluated in humans. Recently, Nuedexta®, a sigma-1 receptor agonist, has been proven to enhance bulbar function in amyotrophic lateral sclerosis (ALS).
The basis for the palliative effect of Nuedexta is speculative. To study this further, the Center for Neurologic Study is collaborating with the Ravits Lab at UCSD to study S1Rs in motor neurons within the hypoglossal and ambiguous nuclei, both of which innervate bulbar musculature. Immunohistochemistry and immunofluorescence are being used to study expression in healthy and various disease phenotypes.