Ligands binding to the prion protein induce its proteolytic release with therapeutic potential in neurodegenerative proteinopathies.

ABSTRACT: The prion protein (PrP^C) is a central player in neurodegenerative diseases, such as prion diseases or Alzheimer’s disease. In contrast to disease-promoting cell surface PrP^C, extracellular fragments act neuroprotective by blocking neurotoxic disease-associated protein conformers. Fittingly, PrP^C release by the metalloprotease ADAM10 represents a protective mechanism. We used biochemical, cell biological, morphological, and structural methods to investigate mechanisms stimulating this proteolytic shedding. Shed PrP negatively correlates with prion conversion and is markedly redistributed in murine brain in the presence of prion deposits or amyloid plaques, indicating a sequestrating activity. PrP-directed ligands cause structural changes in PrP^C a

SUBMITTER: Linsenmeier L 

PROVIDER: S-EPMC8612689 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature