Mohsin Shafiq1,2, Saima Zafar3,4, Neelam Younas1, Aneeqa Noor1, Berta Puig2,5, Hermann Clemens Altmeppen2, Matthias Schmitz1, Jakob Matschke2, Isidre Ferrer6, Markus Glatzel2, Inga Zerr1. 1. Department of Neurology, University Medicine Goettingen and German Center for Neurodegenerative Diseases (DZNE), 37075, Goettingen, Germany. 2. Institute of Neuropathology, University Medical Center Hamburg-Eppendorf (UKE), 20246, Hamburg, Germany. 3. Department of Neurology, University Medicine Goettingen and German Center for Neurodegenerative Diseases (DZNE), 37075, Goettingen, Germany. sz_awaan@yahoo.com. 4. Biomedical Engineering and Sciences Department, School of Mechanical and Manufacturing Engineering (SMME), National University of Sciences and Technology (NUST), Islamabad, Pakistan. sz_awaan@yahoo.com. 5. Department of Neurology, Experimental Research in Stroke and Inflammation (ERSI), University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany. 6. Institut de Neuropatologica, Servei Anatomia Patològica, IDIBELL-Hospital Universitari de Bellvitge, Universitat de Barcelona, Carrer Feixa LLarga sn, 08907, Hospitalet de LLobregat, CIBERNED, Barcelona, Spain.
Abstract
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.
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.
Entities:
Keywords:
Actin; Co-immunoprecipitation; Cytoskeleton; G2L2; GAS; Growth arrest specific 2 like 2; Growth arrest specific proteins; PrPC; Prion protein oligomers; Rapidly progressive Alzheimer’s disease; Tubulin; rpAD
Authors: Keith A Josephs; J Eric Ahlskog; Joseph E Parisi; Bradley F Boeve; Brian A Crum; Caterina Giannini; Ronald C Petersen Journal: Arch Neurol Date: 2009-02
Authors: Oriol Grau-Rivera; Ellen Gelpi; Carlos Nos; Carles Gaig; Isidro Ferrer; Albert Saiz; Albert Lladó; José L Molinuevo; Francesc Graus; Raquel Sánchez-Valle Journal: Neurodegener Dis Date: 2015-10-31 Impact factor: 2.977