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cc by (c) Shafiq et al., 2021
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/174825

Prion protein oligomers cause neuronal cytoskeletal damage in rapidly progressive Alzheimer’s disease

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Background: High-density oligomers of the prion protein (HDPs) have previously been identified in brain tissues of patients with rapidly progressive Alzheimer's disease (rpAD). The current investigation aims at identifying interacting partners of HDPs in the rpAD brains to unravel the pathological involvement of HDPs in the rapid progression. Methods: HDPs from the frontal cortex tissues of rpAD brains were isolated using sucrose density gradient centrifugation. Proteins interacting with HDPs were identified by co-immunoprecipitation coupled with mass spectrometry. Further verifications were carried out using proteomic tools, immunoblotting, and confocal laser scanning microscopy. Results: We identified rpAD-specific HDP-interactors, including the growth arrest specific 2-like 2 protein (G2L2). Intriguingly, rpAD-specific disturbances were found in the localization of G2L2 and its associated proteins i.e., the end binding protein 1, α-tubulin, and β-actin. Discussion: The results show the involvement of HDPs in the destabilization of the neuronal actin/tubulin infrastructure. We consider this disturbance to be a contributing factor for the rapid progression in rpAD.

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SHAFIQ, Mohsin, ZAFAR, Saima, YOUNAS, Neelam, NOOR, Aneeqa, PUIG, Berta, ALTMEPPEN, Hermann clemens, SCHMITZ, Matthias, MATSCHKE, Jakob, FERRER, Isidro (ferrer abizanda), GLATZEL, Markus, ZERR, Inga. Prion protein oligomers cause neuronal cytoskeletal damage in rapidly progressive Alzheimer’s disease. _Molecular Neurodegeneration_. 2021. Vol. 16. [consulta: 10 de gener de 2026]. [Disponible a: https://hdl.handle.net/2445/174825]

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