title: Dissecting the role of sortilin receptor signaling in neurodegeneration induced by NGF deprivation.
abstract: Sortilin is a member of the family of vacuolar protein sorting 10 protein domain receptors which has emerged as a co-receptor in cell death and neurodegeneration processes mediated by proneurotrophins. Here we tested the possibility that sortilin deficiency interferes with behavioral and neuropathological endpoints in a chronic Nerve Growth factor (NGF)-deprivation model of Alzheimer's disease (AD), the AD10 anti-NGF mouse. AD10 mice show cholinergic deficit, increased APP processing and tau hyper-phosphorylation, resulting in behavioral deficits in learning and memory paradigms assessed by novel object recognition and Morris water maze tests. Sort1(-/-) mice were crossed with AD10 anti-NGF mice and the neurodegenerative phenotype was studied. We found that the loss of sortilin partially protected AD10 anti-NGF mice from neurodegeneration. A protective effect was observed on non-spatial memory as assessed by novel object recognition, and histopathologically at the level of Aβ and BFCNs, while the phosphotau increase was unaltered by knocking out sortilin. We suggest that sortilin might be involved in different aspects of neurodegeneration in a complex way, supporting the view that sortilin functions in the CNS are broader than being a co-receptor in proneurotrophin and neurotrophin signaling.
authors: Laboratory of Neurobiology, Scuola Normale Superiore, Pisa, Italy.
authors: Simona
authors: S
authors: Capsoni
authors: Gianluca
authors: G
authors: Amato
authors: Domenico
authors: D
authors: Vignone
authors: Chiara
authors: C
authors: Criscuolo
authors: Anders
authors: A
authors: Nykjaer
authors: Antonino
authors: A
authors: Cattaneo
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000502:physiology*; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D002794:Choline / Q000378:metabolism; D059329:Cholinergic Neurons / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D008569:Memory Disorders / Q000235:genetics; D051379:Mice; D008817:Mice, Mutant Strains; D020932:Nerve Growth Factor / Q000172:deficiency*; D009443:Neuritis / Q000235:genetics; D010766:Phosphorylation; D046188:Protein Modification, Translational; D020917:Receptor, trkA / Q000096:biosynthesis; D015398:Signal Transduction; D016875:tau Proteins / Q000378:metabolism; D000099183:Sortilin
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D016564:Amyloid beta-Protein Precursor; D002794:Choline; D020932:Nerve Growth Factor; D020917:Receptor, trkA; D016875:tau Proteins; D000099183:Sortilin; C558298:Mapt protein, mouse