title: The implications of sortilin/vps10p domain receptors in neurological and human diseases.
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.
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: Wilson
authors.forename: Thomas
authors.initials: T
authors.lastname: Naves
authors.forename: Sofiane
authors.initials: S
authors.lastname: Saada
authors.forename: Sandra
authors.initials: S
authors.lastname: Pinet
authors.forename: François
authors.initials: F
authors.lastname: Vincent
authors.forename: Fabrice
authors.initials: F
authors.lastname: Lalloué
authors.affiliation: EA3842 Homeostasie cellulaire et pathologies and Chaire de pneumologie experimentale, Université de Limoges, Faculté de Médecine, 2, rue du Dr Raymond Marcland, 87025 Limoges CEDEX, France. cornelia.wilson@unilim.fr.
authors.forename: Marie-Odile
authors.initials: MO
authors.lastname: Jauberteau
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism*; D000818:Animals; D002318:Cardiovascular Diseases / Q000378:metabolism; D006801:Humans; D008659:Metabolic Diseases / Q000378:metabolism*; D009422:Nervous System Diseases / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism; D000099183:Sortilin
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D011956:Receptors, Cell Surface; D000099183:Sortilin