SUMO inhibits Tau aggregation in Alzheimer's disease.

Tau is a microtubule-binding, hydrophilic protein and appears randomly coiled in circular dichroism spectra. Tau can have many post-translational modifications such as phosphorylation, acetylation, SUMOylation, glycation, ubiquitinylation, etc. The abnormal phosphorylation of Tau lowers its affinity to bind the microtubules, causing to neuronal instability. Hyperphosphorylated Tau can get detach from the microtubules and get aggregate in neuronal cell body to form a neurofibrillary tangle, which leads to weaken axonal transport and cause synaptic dysfunction. Tau itself is a SUMO-1 target protein and the modified lysine has been identified as the K340 located within 4R-Tau. The interaction between Tau and SUMO-1 was confirmed by an independent study, by showing that the SUMO-1 immunoreactivity is co-localized with phosphorylated Tau. In addition to this, Tau can also be ubiquitinated and degraded by the proteasome through both ubiquitin-dependent and ubiquitin-independent pathways. Our study shows that SUMOylation at lysine K340 stimulates Tau phosphorylation and inhibits ubiquitination-mediated Tau degradation, thus favouring its aggregation.