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Personalised regional modelling predicts tau progression in the human brain
Aggregation of the hyperphosphorylated tau protein is a central driver of Alzheimer's disease, and its accumulation exhibits a rich spatiotemporal pattern that unfolds during the course of the disease, sequentially progressing through the brain across axonal connections. It is unclear how this spatiotemporal process is orchestrated, namely, to what extent the spread of pathologic tau is governed by transport between brain regions, local production, or both. To address this, we develop a...
Regulation of endothelial cell senescence via the miR-217/FOXO3 axis
The accumulation of senescent endothelial cells within the endothelium leads to vascular dysfunction. Independent studies have linked miR-217, a senescence-associated microRNA and FOXO3, a longevity factor, to cellular senescence in different study models. However, their roles and direct interaction in endothelial replicative senescence (RS) remain to be investigated. This study sought to investigate the role of miR-217/FOXO3 axis in endothelial cell senescence. Young and RS HUVEC models were...
Vitamin D deficiency as a risk factor for cognitive decline in individuals aged 50 or older
Longitudinal studies provide conflicting evidence regarding the impact of vitamin D deficiency on cognitive performance in older individuals. The present study aimed to investigate whether vitamin D deficiency is a risk factor for poorer trajectories in global cognition and specific cognitive domains over a six-year follow-up period. This cohort study analysed data from 2625 participants aged 50 years or older from the English Longitudinal Study of Ageing. Vitamin D [25-hydroxyvitamin D,...
The dual ubiquitin binding mode of SPRTN secures rapid spatiotemporal proteolysis of DNA-protein crosslinks
DNA-protein crosslinks (DPCs) are endogenous and chemotherapy-induced genotoxic DNA lesions and, if not repaired, lead to embryonic lethality, neurodegeneration, premature ageing, and cancer. DPCs are heavily polyubiquitinated, and the SPRTN protease and 26S proteasome emerged as two central enzymes for DPC proteolysis. The proteasome recognizes its substrates by their ubiquitination status. How SPRTN protease, an essential enzyme for DPC proteolysis, achieves specificity for DPCs is still not...
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