Effect of the Sigma-1 receptor on neurite outgrowth

Neurite outgrowth is one of the essential processes underlying development and plasticity of the nervous system. Enhancing neurite outgrowth, along with neural protection, is one of the most prominent therapeutic strategies against neuronal degeneration or damage. The sigma-1 receptor (Sig-1R) is a brain-enriched a receptor chaperone expressed in the ER membrane. As Sig-1R is involved in the mode of action of several neurotherapeutic drugs, it is important to elucidate the molecular mechanism of Sig-1R. This would increase our understanding of the pathology of neuronal diseases as well as aid in establishing new approaches for their treatment. In this review, we focus on the findings that Sig-1R contributes to neural protection and neurite outgrowth even in pathological conditions, such as in high glutamate concentration. Although a large part of molecular mechanisms of Sig-1R remains unknown, the interaction of Sig-1R and neurotrophin receptors has been recently reported. Activation of Sig-1R leads to an increase in the secretion of neurotrophin. Meanwhile, Sig-1R enhances neurotrophin receptor-mediated neurite outgrowth upon activation. We discuss the neurite outgrowth effect of Sig-1R, especially in relation to neurotrophin-mediated neurite outgrowth.