Cathepsin D in a murine model of frontotemporal dementia with Parkinsonism-linked to chromosome 17.
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.
['Fernández-Montoya|Julia|J|', 'Pérez|Mar|M|']
D000367:Age Factors D000818:Animals D002402:Cathepsin D D002886:Chromosomes, Human, Pair 17 D004195:Disease Models, Animal D057180:Frontotemporal Dementia D015971:Gene Expression Regulation, Enzymologic D006624:Hippocampus 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 D016875:tau Proteins
Cathepsin D FTDP-17 lysosomal system mutated tau