title: Cathepsin D in a murine model of frontotemporal dementia with Parkinsonism-linked to chromosome 17.
abstract: Tauopathies, such as Alzheimer's disease (AD) and Frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17), are characterized by tau accumulation. This accumulation could result from alterations in tau degradation by either the ubiquitin-proteasome system or the autophagy-lysosomal pathway. To analyze a possible alteration of the autophagy-lysosomal pathway in transgenic mice expressing human tau with three FTDP-17 missense mutations (TauVLW mice), we studied the lysosomal enzyme Cathepsin D. The hippocampi of TauVLW mice, where the human mutant tau accumulates, showed both increased Cathepsin D and partial colocalization of Cathepsin D with human mutant tau. At the ultrastructural level, some multivesicular bodies showed human mutant tau-immunopositive vesicles. This finding could provide insights into the molecular mechanisms of tau degradation in human tauopathies.
authors.affiliation: Departamento de Anatomía, Histología y Neurociencia, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Julia
authors.initials: J
authors.lastname: Fernández-Montoya
authors.affiliation: Departamento de Anatomía, Histología y Neurociencia, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Mar
authors.initials: M
authors.lastname: Pérez
mesh_terms: D000367:Age Factors; D000818:Animals; D002402:Cathepsin D / Q000378:metabolism*; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D004195:Disease Models, Animal; D057180:Frontotemporal Dementia / Q000235:genetics*; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics*; D006624:Hippocampus / Q000201:enzymology* / Q000473:pathology / Q000648:ultrastructure; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D020125:Mutation, Missense; D009419:Nerve Tissue Proteins / Q000378:metabolism; D016875:tau Proteins / Q000235:genetics
chemical_list: D009419:Nerve Tissue Proteins; D016875:tau Proteins; D002402:Cathepsin D
keywords: Cathepsin D; FTDP-17; lysosomal system; mutated tau