Dataset Information

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

ABSTRACT: Tauopathies are characterized by the progressive accumulation of abnormal tau species, which disrupt the autophagy-lysosomal pathway (ALP), a critical system for degrading intracellular macromolecules and aggregated proteins, causing toxicity and cell death. This study investigates the impact of the N-terminally truncated Tau35 protein overexpression on proteolytic pathways, including effects on autophagy and endo-lysosomal processes. Using a Tau35 mouse model and SH-SY5Y cell lines stably expressing either the Tau35 fragment or full-length tau, we employed western blotting, proteomic analysis of lysosome-enriched brain fractions, proteolysis/endocytosis assays, and live-cell imaging with the lysotracker reporter to assess protein degradation and lysosomal function. Our findings identify early pathological changes in endo-lysosomal processes, including increased endocytosis, proteolytic dysfunction and lysosomal motility abnormalities, associated with Tau35- induced toxicity.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

SUBMITTER: Steven Lynham

LAB HEAD: Prof. Deepak Srivastava

PROVIDER: PXD062128 | Pride | 2025-12-22

REPOSITORIES: Pride

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Dataset's files

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			Action	DRS
	PR723_DG4_10_S1_Tg2.mzid	Mzid
	PR723_DG4_10_S1_Tg2.mzid_PR723_DG4_10_S1_Tg2.MGF	Mzid
	PR723_DG4_10_S1_Tg2.raw	Raw
	PR723_DG4_11_S1_Tg3.mzid	Mzid
	PR723_DG4_11_S1_Tg3.mzid_PR723_DG4_11_S1_Tg3.MGF	Mzid

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

Goniotaki Despoina D Hausherr Maximilian M Lynham Steven S Ale Ayushin A Chennell George G Marcotti Stefania S Marcus Katrin K Noble Wendy W Hanger Diane P DP Fraser Graham G Srivastava Deepak P DP

Alzheimer's & dementia : the journal of the Alzheimer's Association 20251201 12

<h4>Introduction</h4>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.<h4>Methods</h4>Using the Tau35 mouse model and SH-SY5Y human neuroblastoma cells stably exp ...[more]

PMID: 41399158

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