The role of reticulons in neurodegenerative diseases.
Reticulons (RTNs) are a group of membrane-associated proteins mainly responsible for shaping the tubular endoplasmic reticulum network, membrane trafficking, inhibition of axonal growth, and apoptosis. These proteins share a common sequence feature, the reticulon homology domain, which consists of paired hydrophobic stretches that are believed to induce membrane curvature by acting as a wedge in bilayer membranes. RTNs are ubiquitously expressed in all tissues, but each RTN member exhibits a unique expression pattern that prefers certain tissues or even cell types. Recently, accumulated evidence has suggested additional and unexpected roles for RTNs, including those on DNA binding, autophagy, and several inflammatory-related functions. These manifold actions of RTNs account for their ever-growing recognition of their involvement in neurodegenerative diseases like Alzheimer's disease, amyotrophic lateral sclerosis, multiple sclerosis, as well as hereditary spastic paraplegia. This review summarizes the latest discoveries on RTNs in human pathophysiology, and the engagement of these in neurodegeneration, along with the implications of these findings for a better understanding of the molecular events triggered by RTNs and their potential exploitation as next-generation therapeutics.
Laboratorio di Neurochimica dei Lipidi, Centro Europeo di Ricerca sul Cervello (CERC) - Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Santa Lucia, Rome, Italy.
Valerio
V
Chiurchiù
Mauro
M
Maccarrone
Antonio
A
Orlacchio
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001343:Autophagy / Q000502:physiology; D002352:Carrier Proteins / Q000502:physiology; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000648:ultrastructure; D005544:Forecasting; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007425:Intracellular Membranes / Q000378:metabolism / Q000648:ultrastructure; D008565:Membrane Proteins / Q000502:physiology; D005810:Multigene Family; D009185:Myelin Proteins / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000145:classification / Q000502:physiology*; D019636:Neurodegenerative Diseases / Q000378:metabolism*; D055495:Neurogenesis / Q000502:physiology; D000070798:Nogo Proteins; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship
D002352:Carrier Proteins; D008565:Membrane Proteins; D009185:Myelin Proteins; D009419:Nerve Tissue Proteins; D000070798:Nogo Proteins; C081781:RTN1 protein, human; C476198:RTN3 protein, human; C000603199:RTN4 protein, human