The transglutaminase-2 interactome in the APP23 mouse model of Alzheimer’s disease

Wilhelmus, MMM, Tonoli, E ORCID: https://orcid.org/0000-0001-9774-1048, Coveney, C ORCID: https://orcid.org/0000-0001-7047-6408, Boocock, DJ ORCID: https://orcid.org/0000-0002-7333-3549, Jongenelen, CAM, Brevé, JJP, Verderio, EAM ORCID: https://orcid.org/0000-0001-9153-8997 and Drukarch, B, 2022. The transglutaminase-2 interactome in the APP23 mouse model of Alzheimer’s disease. Cells, 11 (3): 389. ISSN 2073-4409

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Abstract

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.

Item Type:	Journal article
Publication Title:	Cells
Creators:	Wilhelmus, M.M.M., Tonoli, E., Coveney, C., Boocock, D.J., Jongenelen, C.A.M., Brevé, J.J.P., Verderio, E.A.M. and Drukarch, B.
Publisher:	MDPI AG
Date:	24 January 2022
Volume:	11
Number:	3
ISSN:	2073-4409
Identifiers:	Number Type 10.3390/cells11030389 DOI 1516717 Other
Rights:	© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Divisions:	Schools > School of Science and Technology
Record created by:	Laura Ward
Date Added:	11 Feb 2022 14:46
Last Modified:	11 Feb 2022 14:46
URI:	https://irep.ntu.ac.uk/id/eprint/45632

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