TY  - JOUR
AU  - Shafiq, Mohsin
AU  - Zafar, Saima
AU  - Younas, Neelam
AU  - Noor, Aneeqa
AU  - Puig, Berta
AU  - Altmeppen, Hermann Clemens
AU  - Schmitz, Matthias
AU  - Matschke, Jakob
AU  - Ferrer, Isidre
AU  - Glatzel, Markus
AU  - Zerr, Inga
TI  - Prion protein oligomers cause neuronal cytoskeletal damage in rapidly progressive Alzheimer's disease.
JO  - Molecular neurodegeneration
VL  - 16
IS  - 1
SN  - 1750-1326
CY  - London
PB  - Biomed Central
M1  - DZNE-2021-00789
SP  - 11
PY  - 2021
AB  - 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.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.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.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.
KW  - Alzheimer Disease: metabolism
KW  - Amyloid beta-Peptides: metabolism
KW  - Brain: metabolism
KW  - Cytoskeleton: metabolism
KW  - Cytoskeleton: pathology
KW  - Disease Progression
KW  - Humans
KW  - Neurons: metabolism
KW  - Prion Proteins: metabolism
KW  - Actin (Other)
KW  - Co-immunoprecipitation (Other)
KW  - Cytoskeleton (Other)
KW  - G2L2 (Other)
KW  - GAS (Other)
KW  - Growth arrest specific 2 like 2 (Other)
KW  - Growth arrest specific proteins (Other)
KW  - PrPC (Other)
KW  - Prion protein oligomers (Other)
KW  - Rapidly progressive Alzheimer’s disease (Other)
KW  - Tubulin (Other)
KW  - rpAD (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:33618749
C2  - pmc:PMC7898440
DO  - DOI:10.1186/s13024-021-00422-x
UR  - https://pub.dzne.de/record/155621
ER  -