Title:The Implications of Sortilin/Vps10p Domain Receptors in Neurological and Human Diseases
Volume: 13
Issue: 8
Author(s): Cornelia M. Wilson, Thomas Naves, Sofiane Saada, Sandra Pinet, Francois Vincent, Fabrice Lalloue and Marie-Odile Jauberteau
Affiliation:
Keywords:
Alzheimer's disease, cancer, Parkinson disease, sortilin, type 2 diabetes mellitus, vacuolar protein sorting 10
protein.
Abstract: The neurotensin receptor-3 also known as sortilin is part of the new receptor family of vacuolar protein sorting
10 protein domain. Growing evidence show that the vacuolar protein sorting 10 protein domain family is implicated as a
genetic risk factor for neurodegenerative diseases such as Alzheimer’s disease, frontotemporal lobar degeneration, and
Parkinson's disease, in addition to links associated with type 2 diabetes mellitus, lysosomal disorders, cardiovascular
disease and atherosclerosis. In fact, sortilin expression is elevated in many human cell lines controlling the trafficking and
release of neurotrophins. Hence, not surprisingly the imbalance of neurotrophin signaling is implicated in several human
diseases. The fine regulation of the growth factor, brain derived nerve factor by sortilin mediates both neuronal and tumor
cell survival, whereas in Alzheimer’s disease sortilin mediated beta secretase-1 trafficking increases the cleavage of the
beta-amyloid precursor protein. Perturbation of the autocrine/paracrine loop of neurotrophins in combination with the cell
surface interaction of sortilin with neurotensin receptor 1 or 2 or tyrosine kinase receptor A or B are dramatically
upregulated in both neurodegenerative diseases and cancer. In cardiovascular diseases, the circulatory low-density
lipoprotein is closely correlated with sortilin expression in hepatocytes. Herein, this review discusses the multifaceted role
played by sortilin and its interacting partners in human disease which could be interesting novel target(s) in drug
discovery. Nevertheless, completely challenging the function of sortilin could prove unfavorable given the important
universal role of sortilin plays in the body. Hence, metabolism disorders could be relieved with specific targeted
therapeutic challenge of sortilin function.