2026-04-14T18:12:38Zhttps://uvadoc.uva.es/oai/request

oai:uvadoc.uva.es:10324/638962025-01-13T07:36:16Zcom_10324_1134com_10324_931com_10324_894col_10324_1213

Yang, Yun Tapias Molina, Victor Acosta, Diana Xu, Hui Chen, Huanlian Bhawal, Ruchika Anderson, Elizabeth T. Ivanova, Elena Lin, Hening Sagdullaev, Botir T. Chen, Jianer Klein, William L. Viola, Kirsten L. Gandy, Sam Haroutunian, Vahram Beal, M. Flint Eliezer, David Zhang, Sheng Gibson, Gary E. 2024-01-02T01:25:35Z 2024-01-02T01:25:35Z 2022 Nature Communications, Enero 2022, vol. 13, n. 1. p. 159 https://uvadoc.uva.es/handle/10324/63896 10.1038/s41467-021-27572-2 1 Nature Communications 13 2041-1723 Abnormalities in brain glucose metabolism and accumulation of abnormal protein deposits called plaques and tangles are neuropathological hallmarks of Alzheimer’s disease (AD), but their relationship to disease pathogenesis and to each other remains unclear. Here we show that succinylation, a metabolism-associated post-translational protein modification (PTM), provides a potential link between abnormal metabolism and AD pathology. We quantified the lysine succinylomes and proteomes from brains of individuals with AD, and healthy controls. In AD, succinylation of multiple mitochondrial proteins declined, and succinylation of small number of cytosolic proteins increased. The largest increases occurred at critical sites of amyloid precursor protein (APP) and microtubule-associated tau. We show that in vitro, succinylation of APP disrupted its normal proteolytic processing thereby promoting Aβ accumulation and plaque formation and that succinylation of tau promoted its aggregation to tangles and impaired microtubule assembly. In transgenic mouse models of AD, elevated succinylation associated with soluble and insoluble APP derivatives and tau. These findings indicate that a metabolism-linked PTM may be associated with AD. eng info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/4.0/ Atribución 4.0 Internacional Altered succinylation of mitochondrial proteins, APP and tau in Alzheimer’s disease info:eu-repo/semantics/article