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000473388 1001_ $$0P:(DE-HGF)0$$aLinsenmeier, Luise$$b0
000473388 245__ $$aLigands binding to the prion protein induce its proteolytic release with therapeutic potential in neurodegenerative proteinopathies
000473388 260__ $$aWashington, DC [u.a.]$$bAssoc.$$c2021
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000473388 520__ $$aThe prion protein (PrPC) is a central player in neurodegenerative diseases, such as prion diseases or Alzheimer’sdisease. In contrast to disease-promoting cell surface PrPC, extracellular fragments act neuroprotective by blockingneurotoxic disease-associated protein conformers. Fittingly, PrPC release by the metalloprotease ADAM10represents a protective mechanism. We used biochemical, cell biological, morphological, and structural methodsto investigate mechanisms stimulating this proteolytic shedding. Shed PrP negatively correlates with prion conversionand is markedly redistributed in murine brain in the presence of prion deposits or amyloid plaques, indicatinga sequestrating activity. PrP-directed ligands cause structural changes in PrPC and increased shedding in cellsand organotypic brain slice cultures. As an exception, some PrP-directed antibodies targeting repetitive epitopesdo not cause shedding but surface clustering, endocytosis, and degradation of PrPC. Both mechanisms may contributeto beneficial actions described for PrP-directed ligands and pave the way for new therapeutic strategiesagainst currently incurable neurodegenerative diseases.
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000473388 7001_ $$0P:(DE-HGF)0$$aMohammadi, Behnam$$b1
000473388 7001_ $$0P:(DE-HGF)0$$aShafiq, Mohsin$$b2
000473388 7001_ $$00000-0002-0945-8857$$aFrontzek, Karl$$b3
000473388 7001_ $$aBär, Julia$$b4
000473388 7001_ $$00000-0002-1322-8018$$aShrivastava, Amulya N.$$b5
000473388 7001_ $$aDamme, Markus$$b6
000473388 7001_ $$aSong, Feizhi$$b7
000473388 7001_ $$00000-0002-9700-9129$$aSchwarz, Alexander$$b8
000473388 7001_ $$0P:(DE-HGF)0$$aDa Vela, Stefano$$b9
000473388 7001_ $$00000-0002-6176-2696$$aMassignan, Tania$$b10
000473388 7001_ $$00000-0002-0365-5710$$aJung, Sebastian$$b11
000473388 7001_ $$aCorreia, Angela$$b12
000473388 7001_ $$00000-0002-5502-681X$$aSchmitz, Matthias$$b13
000473388 7001_ $$00000-0002-2255-8393$$aPuig, Berta$$b14
000473388 7001_ $$00000-0002-2674-9891$$aHornemann, Simone$$b15
000473388 7001_ $$aZerr, Inga$$b16
000473388 7001_ $$00000-0001-5017-5528$$aTatzelt, Jörg$$b17
000473388 7001_ $$aBiasini, Emiliano$$b18
000473388 7001_ $$aSaftig, Paul$$b19
000473388 7001_ $$aSchweizer, Michaela$$b20
000473388 7001_ $$0P:(DE-H253)PIP1001422$$aSvergun, Dmitri$$b21
000473388 7001_ $$0P:(DE-HGF)0$$aAmin, Ladan$$b22
000473388 7001_ $$aMazzola, Federica$$b23
000473388 7001_ $$00000-0002-0963-0987$$aVarani, Luca$$b24
000473388 7001_ $$aThapa, Simrika$$b25
000473388 7001_ $$aGilch, Sabine$$b26
000473388 7001_ $$00000-0003-4972-8740$$aSchätzl, Hermann$$b27
000473388 7001_ $$00000-0002-6985-5790$$aHarris, David A.$$b28
000473388 7001_ $$aTriller, Antoine$$b29
000473388 7001_ $$aMikhaylova, Marina$$b30
000473388 7001_ $$00000-0002-0344-6708$$aAguzzi, Adriano$$b31
000473388 7001_ $$0P:(DE-HGF)0$$aAltmeppen, Hermann C.$$b32$$eCorresponding author
000473388 7001_ $$00000-0002-7720-8817$$aGlatzel, Markus$$b33$$eCorresponding author
000473388 773__ $$0PERI:(DE-600)2810933-8$$a10.1126/sciadv.abj1826$$gVol. 7, no. 48, p. eabj1826$$n48$$peabj1826$$tScience advances$$v7$$x2375-2548$$y2021
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