Issue Cover (November 2020)

Front cover: The aberrant phosphorylation of tau protein at threonine Thr175 is a pathologic event that promotes the formation of tau fibrils both in vitro and in vivo. Previous research has shown that this fibril formation is dependant upon the activation of glycogen synthase kinase 3β (GSK3β) via a previously unknown mechanism. The phosphorylation of tau at Thr175 occurs acutely following traumatic brain injury in rats and results in the aberrant exposure of the tau N‐terminal phosphatase‐activating domain (PAD). This event activates protein phosphatase 1 (PP1), which then removes an inhibitory phosphate from the Ser9 residue of GSK3β, leading to its activation. This research contributes to our understanding of how initial aberrant modifications to tau protein in neuronal injury can contribute to further propagation of tauopathy in a variety of neurodegenerative conditions. Image content : Live cell imaging of HEK293T cell expressing pseudophosphorylated (Thr175Asp) eGFP‐tagged tau protein. Dense curvilinear fibrils are visible within the cell.Read the full article   ‘Tau protein phosphorylation at Thr 175 initiates fibril formation via accessibility of the N‐terminal phosphatase‐activating domain’ by M. A. Hintermayer, K. Volkening, A. J. Moszczynski, N. Donison, M. J. Strong, ( J. Neurochem. 2020, vol. 155 (3), pp. 313–326) on doi: 10.1111/jnc.14942