"S-Tau-Lled" Lysosomes Disrupt Autophagic Processes in Neurodegeneration.

IF 2.8 3区生物学 Q3 CELL BIOLOGY

Traffic Pub Date : 2026-09-01 DOI:10.1111/tra.70051

Anaïs Bécot, Mehdi Kabani

引用次数: 0

Abstract

Tauopathies are a class of neurodegenerative diseases characterized by the accumulation of hyperphosphorylated, misfolded and aggregated Tau proteins and by dysfunctions in the autophagy-lysosome system. Whether the latter are a cause or a consequence of the former is unclear. The answer may come from a recent study by Mirfakhar et al. Using human iPSC-derived neurons harboring the MAPT p.R406W mutation in Tau, they were able to show that pathogenic Tau is able to broadly impair lysosomal function ahead of Tau accumulation. They also show that the degradative function of lysosomes, but not their motility, can be restored through pharmacological activation of autophagy, leading to reduced Tau levels. This work opens new therapeutic opportunities to eliminate early-on pathological misfolded Tau proteins before they can engage in a vicious cycle of aggregation, amplification and propagation.

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“s - tau - lll”溶酶体破坏神经退行性疾病的自噬过程。

Tau病是一类神经退行性疾病，其特征是过度磷酸化，错误折叠和聚集的Tau蛋白的积累以及自噬溶酶体系统的功能障碍。后者是前者的原因还是结果尚不清楚。答案可能来自Mirfakhar等人最近的一项研究。利用人类ipsc衍生的Tau蛋白中含有MAPT p.R406W突变的神经元，他们能够证明致病性Tau蛋白能够在Tau蛋白积累之前广泛损害溶酶体功能。他们还表明，溶酶体的降解功能，而不是它们的运动，可以通过自噬的药理激活恢复，导致Tau水平降低。这项工作开辟了新的治疗机会，在早期病理性错误折叠的Tau蛋白参与聚集、扩增和繁殖的恶性循环之前消除它们。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Traffic 生物-细胞生物学

CiteScore

8.10

自引率

2.20%

发文量

审稿时长

2 months

期刊介绍： Traffic encourages and facilitates the publication of papers in any field relating to intracellular transport in health and disease. Traffic papers span disciplines such as developmental biology, neuroscience, innate and adaptive immunity, epithelial cell biology, intracellular pathogens and host-pathogen interactions, among others using any eukaryotic model system. Areas of particular interest include protein, nucleic acid and lipid traffic, molecular motors, intracellular pathogens, intracellular proteolysis, nuclear import and export, cytokinesis and the cell cycle, the interface between signaling and trafficking or localization, protein translocation, the cell biology of adaptive an innate immunity, organelle biogenesis, metabolism, cell polarity and organization, and organelle movement. All aspects of the structural, molecular biology, biochemistry, genetics, morphology, intracellular signaling and relationship to hereditary or infectious diseases will be covered. Manuscripts must provide a clear conceptual or mechanistic advance. The editors will reject papers that require major changes, including addition of significant experimental data or other significant revision. Traffic will consider manuscripts of any length, but encourages authors to limit their papers to 16 typeset pages or less.