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Article

The Transglutaminase-2 Interactome in the APP23 Mouse Model of Alzheimer’s Disease

1
Department of Anatomy and Neurosciences, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HZ Amsterdam, The Netherlands
2
School of Science and Technology, Nottingham Trent University, Nottingham NG11 8NS, UK
3
Department of Biological Sciences, Alma Mater Studiorum University of Bologna, 40126 Bologna, Italy
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Dora Brites
Cells 2022, 11(3), 389; https://doi.org/10.3390/cells11030389
Received: 14 December 2021 / Revised: 6 January 2022 / Accepted: 14 January 2022 / Published: 24 January 2022
Amyloid-beta (Aβ) deposition in the brain is closely linked with the development of Alzheimer’s disease (AD). Unfortunately, therapies specifically targeting Aβ deposition have failed to reach their primary clinical endpoints, emphasizing the need to broaden the search strategy for alternative targets/mechanisms. Transglutaminase-2 (TG2) catalyzes post-translational modifications, is present in AD lesions and interacts with AD-associated proteins. However, an unbiased overview of TG2 interactors is lacking in both control and AD brain. Here we aimed to identify these interactors using a crossbreed of the AD-mimicking APP23 mouse model with wild type and TG2 knock-out (TG2−/−) mice. We found that absence of TG2 had no (statistically) significant effect on Aβ pathology, soluble brain levels of Aβ1–40 and Aβ1–42, and mRNA levels of TG family members compared to APP23 mice at 18 months of age. Quantitative proteomics and network analysis revealed a large cluster of TG2 interactors involved in synaptic transmission/assembly and cell adhesion in the APP23 brain typical of AD. Comparative proteomics of wild type and TG2−/− brains revealed a TG2-linked pathological proteome consistent with alterations in both pathways. Our data show that TG2 deletion leads to considerable network alterations consistent with a TG2 role in (dys)regulation of synaptic transmission and cell adhesion in APP23 brains. View Full-Text
Keywords: transglutaminase-2; Alzheimer’s disease; amyloid-beta; interactome; mouse model transglutaminase-2; Alzheimer’s disease; amyloid-beta; interactome; mouse model
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MDPI and ACS Style

Wilhelmus, M.M.M.; Tonoli, E.; Coveney, C.; Boocock, D.J.; Jongenelen, C.A.M.; Brevé, J.J.P.; Verderio, E.A.M.; Drukarch, B. The Transglutaminase-2 Interactome in the APP23 Mouse Model of Alzheimer’s Disease. Cells 2022, 11, 389. https://doi.org/10.3390/cells11030389

AMA Style

Wilhelmus MMM, Tonoli E, Coveney C, Boocock DJ, Jongenelen CAM, Brevé JJP, Verderio EAM, Drukarch B. The Transglutaminase-2 Interactome in the APP23 Mouse Model of Alzheimer’s Disease. Cells. 2022; 11(3):389. https://doi.org/10.3390/cells11030389

Chicago/Turabian Style

Wilhelmus, Micha M.M., Elisa Tonoli, Clare Coveney, David J. Boocock, Cornelis A.M. Jongenelen, John J.P. Brevé, Elisabetta A.M. Verderio, and Benjamin Drukarch. 2022. "The Transglutaminase-2 Interactome in the APP23 Mouse Model of Alzheimer’s Disease" Cells 11, no. 3: 389. https://doi.org/10.3390/cells11030389

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