RT info:eu-repo/semantics/article
T1 Altered succinylation of mitochondrial proteins, APP and tau in Alzheimer’s disease
A1 Yang, Yun
A1 Tapias, Victor
A1 Acosta, Diana
A1 Xu, Hui
A1 Chen, Huanlian
A1 Bhawal, Ruchika
A1 Anderson, Elizabeth T.
A1 Ivanova, Elena
A1 Lin, Hening
A1 Sagdullaev, Botir T.
A1 Chen, Jianer
A1 Klein, William L.
A1 Viola, Kirsten L.
A1 Gandy, Sam
A1 Haroutunian, Vahram
A1 Beal, M. Flint
A1 Eliezer, David
A1 Zhang, Sheng
A1 Gibson, Gary E.
AB 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.
YR 2022
FD 2022
LK https://uvadoc.uva.es/handle/10324/63896
UL https://uvadoc.uva.es/handle/10324/63896
LA eng
NO Nature Communications, Enero 2022, vol. 13, n. 1. p. 159
NO Producción Científica
DS UVaDOC
RD 23-nov-2024