Ligands binding to the prion protein induce its proteolytic release with therapeutic potential in neurodegenerative proteinopathies.
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ABSTRACT:
SUBMITTER: Linsenmeier L
PROVIDER: S-EPMC8612689 | biostudies-literature | 2021 Nov
REPOSITORIES: biostudies-literature
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Ligands binding to the prion protein induce its proteolytic release with therapeutic potential in neurodegenerative proteinopathies.
Linsenmeier Luise L Mohammadi Behnam B Shafiq Mohsin M Frontzek Karl K Bär Julia J Shrivastava Amulya N AN Damme Markus M Song Feizhi F Schwarz Alexander A Da Vela Stefano S Massignan Tania T Jung Sebastian S Correia Angela A Schmitz Matthias M Puig Berta B Hornemann Simone S Zerr Inga I Tatzelt Jörg J Biasini Emiliano E Saftig Paul P Schweizer Michaela M Svergun Dmitri D Amin Ladan L Mazzola Federica F Varani Luca L Thapa Simrika S Gilch Sabine S Schätzl Hermann H Harris David A DA Triller Antoine A Mikhaylova Marina M Aguzzi Adriano A Altmeppen Hermann C HC Glatzel Markus M
Science advances 20211124 48
The prion protein (PrP<sup>C</sup>) is a central player in neurodegenerative diseases, such as prion diseases or Alzheimer’s disease. In contrast to disease-promoting cell surface PrP<sup>C</sup>, extracellular fragments act neuroprotective by blocking neurotoxic disease-associated protein conformers. Fittingly, PrP<sup>C</sup> release by the metalloprotease ADAM10 represents a protective mechanism. We used biochemical, cell biological, morphological, and structural methods to investigate mechan ...[more]
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