Cathepsin D in a Murine Model of Frontotemporal Dementia with Parkinsonism-Linked to Chromosome 17
Cathepsin D in a Murine Model of Frontotemporal Dementia with Parkinsonism-Linked to Chromosome 17
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DOI：
10.3233/jad-140456
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发表时间：
2015-01-01
影响因子：
4
通讯作者：
Perez, Mar
中科院分区：
文献类型：
--
作者：
Fernandez-Montoya, Julia;Perez, Mar
tau 蛋白病，例如阿尔茨海默病 (AD) 和 17 号染色体相关帕金森病额颞叶痴呆 (FTDP-17)，其特点是 tau 蛋白积累。这种积累可能是由于泛素-蛋白酶体系统或自噬-溶酶体途径引起的 tau 蛋白降解变化所致。为了分析表达具有三个 FTDP-17 错义突变的人 tau 的转基因小鼠（Tau(VLW) 小鼠）中自噬-溶酶体途径可能发生的改变，我们研究了溶酶体酶组织蛋白酶 D。 Tau(VLW) 小鼠的海马（人突变 tau 积累的地方）显示出组织蛋白酶 D 增加以及组织蛋白酶 D 与人突变 tau 的部分共定位。在超微结构水平上，一些多囊泡体显示出人类突变型 tau 免疫阳性囊泡。这一发现可以为人类 tau 蛋白病中 tau 蛋白降解的分子机制提供见解。
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 (Tau(VLW) mice), we studied the lysosomal enzyme Cathepsin D. The hippocampi of Tau(VLW) 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.