Reticulon Protein-1C: A New Hope in the Treatment of Different Neuronal Diseases

Abstract

Reticulons (RTNs) are a group of membrane proteins localized on the ER and known to regulate ER structure and functions. Several studies have suggested that RTNs are involved in different important cellular functions such as changes in calcium homeostasis, ER-stress-mediated cell death, and autophagy. RTNs have been demonstrated to exert a cancer specific proapoptotic function via the interaction or the modulation of specific proteins. Reticulons have also been implicated in different signaling pathways which are at the basis of the pathogenesis of several neurodegenerative diseases. In this paper we discuss the accumulating evidence identifying RTN-1C protein as a promising target in the treatment of different pathologies such as cancer or neurodegenerative disorders.

Figure 1

(a) Scheme showing the reticulons distribution on endoplasmic reticulum and the physical connection between nuclear envelope and ER membrane. (b) Schematic diagram of RTN-1C and histone H4 proteins showing the shared GAKRH motif. The blue aminoacids indicate the two hydrophobic segments of RTN-1C protein. The red aminoacids indicate the three positive charges in the H4 consensus motif. RTN-1C is acetylated on Lys 204.

Figure 2

Schematic representation of the different RTN-1C-induced signaling pathways. Modulation of RTN-1C expression triggers the ER stress pathway and the regulation of different proteins (green ovals) at different levels (blue boxes). These events affect cellular processes (red boxes) which are at the basis of several human pathological settings (grey boxes).