Regulation of tau internalization, degradation, and seeding by LRP1 reveals multiple pathways for tau catabolism.

ABSTRACT: In Alzheimer's disease (AD), pathological forms of tau are transferred from cell to cell and "seed" aggregation of cytoplasmic tau. Phosphorylation of tau plays a key role in neurodegenerative tauopathies. In addition, apolipoprotein E (apoE), a major component of lipoproteins in the brain, is a genetic risk determinant for AD. The identification of the apoE receptor, low-density lipoprotein receptor-related protein 1 (LRP1), as an endocytic receptor for tau raises several questions about the role of LRP1 in tauopathies: is internalized tau, like other LRP1 ligands, delivered to lysosomes for degradation, and does LRP1 internalize pathological tau leading to cytosolic seeding? We found that LRP1 rapidly internalizes ¹²⁵I-labeled tau, which is then efficiently degraded in lysosom

SUBMITTER: Cooper JM 

PROVIDER: S-EPMC8164048 | biostudies-literature | 2021 Jan-Jun

REPOSITORIES: biostudies-literature