Proteomic analysis links truncated tau to lysosome motility, autophagy, and endo-lysosomal dysfunction.

ABSTRACT:

Introduction

Tauopathies involve progressive accumulation of abnormal tau species that disrupt the autophagy-lysosomal pathway (ALP), critical for degrading intracellular macromolecules and aggregates, leading to toxicity and cell death. This study examines how overexpression of the N-terminally truncated Tau35 protein affects proteolytic pathways, including autophagy and endo-lysosomal processes.

Methods

Using the Tau35 mouse model and SH-SY5Y human neuroblastoma cells stably expressing Tau35 or full-length tau, we assessed protein degradation and lysosomal function via Western blotting, proteomics of lysosome-enriched brain fractions, cathepsin activity assays, endocytosis/proteolysis assays, and live-cell imaging using LysoTracker.

Results

We identified early endo-

SUBMITTER: Goniotaki D 

PROVIDER: S-EPMC12706120 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature