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

Molecular Neurodegeneration

Aneeqa Noor¹  Inga Zerr¹  Neelam Younas¹  Matthias Schmitz¹  Saima Zafar²  Mohsin Shafiq³  Isidre Ferrer⁴  Jakob Matschke⁵  Hermann Clemens Altmeppen⁵  Markus Glatzel⁵  Berta Puig⁶ 

[1] Department of Neurology, University Medicine Goettingen and German Center for Neurodegenerative Diseases (DZNE), 37075, Goettingen, Germany;Department of Neurology, University Medicine Goettingen and German Center for Neurodegenerative Diseases (DZNE), 37075, Goettingen, Germany;Biomedical Engineering and Sciences Department, School of Mechanical and Manufacturing Engineering (SMME), National University of Sciences and Technology (NUST), Islamabad, Pakistan;Department of Neurology, University Medicine Goettingen and German Center for Neurodegenerative Diseases (DZNE), 37075, Goettingen, Germany;Institute of Neuropathology, University Medical Center Hamburg-Eppendorf (UKE), 20246, Hamburg, Germany;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;Institute of Neuropathology, University Medical Center Hamburg-Eppendorf (UKE), 20246, Hamburg, Germany;Institute of Neuropathology, University Medical Center Hamburg-Eppendorf (UKE), 20246, Hamburg, Germany;Department of Neurology, Experimental Research in Stroke and Inflammation (ERSI), University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany;

关键词: Rapidly progressive Alzheimer’s disease;    rpAD;    Growth arrest specific proteins;    GAS;    Growth arrest specific 2 like 2;    G2L2;    Prion protein oligomers;    PrP;    Co-immunoprecipitation;    Cytoskeleton;    Actin;    Tubulin;   

DOI  :  10.1186/s13024-021-00422-x

来源: Springer

【 摘 要 】

BackgroundHigh-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.MethodsHDPs 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.ResultsWe 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.DiscussionThe 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.

【 授权许可】

CC BY