SIRT6-CBP-dependent nuclear Tau accumulation and its role in protein synthesis

• DOI: 10.1016/j.celrep.2021.109035
• Publication Date: 2021-04-27T16:21:09Z
• Authors: Miguel Portillo; Ekaterina Eremenko; Shai Kaluski; Alfredo Garcia-Ve...; Lior Onn; Daniel Stein; Zeev Slobodnik; Adam Zaretsky; Uwe Ueberham; Monica Einav; Martina K. Brückner; Thomas Arendt; Debra Toiber
• Keywords: 0303 health sciences; 03 medical and health sciences; Alzheimer Disease; Protein Biosynthesis; Humans; Sirtuins; tau Proteins

Several neurodegenerative diseases present Tau accumulation as the main pathological marker. post-translational modifications such phosphorylation and acetylation are increased in neurodegeneration. Here, we show that hyper-acetylation at residue 174 increases its own nuclear presence is result of DNA damage signaling or lack SIRT6, both causative Tau-K174ac deacetylated nucleus by SIRT6. However, SIRT6 chronic results accumulation. Once there, it induces global changes gene expression, affecting protein translation, synthesis, energy production. Concomitantly, Alzheimer's disease (AD) case subjects nucleolin a decrease levels. AD levels Tau, particularly Tau-K174ac. Our suggest depletion. We propose toxicity due to stability, accumulation, nucleolar dysfunction.