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Congratulations to Jinxia Lu, Shengnan Zhang and Xiaojuan Ma!
Congratulations to Jinxia, Shengnan and Xiaojua for publishing their work in J. Biol. Chem.!


Abstract: Amyloid aggregation of pathological proteins is closely associated with a variety of neurodegenerative diseases, and α-synuclein (α-syn) deposition and Tau tangles are considered as hallmarks of the diseases, such as Parkinson’s disease (PD) and Alzheimer’s disease (AD), respectively. Intriguingly, α-syn and Tau have been found to co-deposit in the brains of individuals with dementia and Parkinsonism, suggesting a potential role of cross-talk between these two proteins in neurodegenerative pathologies. Here, we show that monomeric α-syn and the two variants of Tau, including Tau23 and K19, synergistically promote amyloid fibrillation, leading to their co-aggregation in vitro. NMR spectroscopy experiments revealed that α-syn uses its highly negatively charged C-terminus to directly interact with both Tau23 and K19. Deletion of the C-terminus effectively abolished its binding to Tau23 and K19 as well as its synergistic effect on promoting their fibrillation. Moreover, an S129D substitution of α-syn, mimicking a C-terminal phosphorylation of Ser-129 in α-syn that commonly overserved in the brains of PD patients with elevated α-syn phosphorylation levels, significantly enhanced the activity of α-syn in facilitating Tau23 and K19 aggregation. These results reveal the molecular basis underlying the direct interaction between α-syn and Tau. We proposed that this interplay might contribute to pathological aggregation and of α-syn and Tau in neurodegenerative diseases.


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