MassIVE MSV000096965

Partial Public PXD060223

A role for the autophagy receptor NBR1 in the degradation of Tau aggregates

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Description

Neurofibrillary tangles (NFTs), comprising hyperphosphorylated and aggregated Tau protein, are a primary neuropathological feature of Alzheimer's Disease (AD). In patients, the formation and spread of NFTs across the brain correlate with cognitive decline. However, the mechanisms driving Tau aggregation and leading to the subsequent neuronal dysfunction are not fully understood. In this study, we explored proteomic and phosphoproteomic changes resulting from the seed-induced aggregation of endogenous Tau in human neurons derived from induced pluripotent stem (iPS) cells. We discovered previously undescribed phosphorylation sites on NBR1, an autophagy receptor, which were significantly altered by Tau aggregation in vitro. We further show that NBR1 directly interacts with phosphorylated Tau and Tau aggregates in various cell models. This interaction is associated with autophagic Tau degradation in HEK cells, and siRNA-mediated knockdown of NBR1 significantly increases Tau aggregate levels in iPS-derived neurons. Additionally, we find that NBR1 specifically interacts with phospho-Tau in human AD brain, underscoring the relevance of our findings to the human disease. These insights provide a deeper understanding of the molecular interactions between autophagy receptors and Tau pathology in AD and reveal a role for NBR1 as an important receptor for pathological forms of Tau. [doi:10.25345/C5JW87068] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: Alzheimer's Disease, Tau aggregation, phospho-proteomics, proteomics, autophagy receptor, Tau, iPS-derived neurons, mass spectrometry ; DatasetType:Proteomics

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Principal Investigators:
(in alphabetical order) 		Marie Neu, Abbvie Deutschland GmbH & Co-KG, Deutschland
Submitting User: MarieNeu
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