Under pathological conditions, tau\u00a0undergoes various aberrant post-translational modifications (PTMs), such as truncation, phosphorylation, ubiquitination, acetylation, glycosylation, etc<\/em>. Among them, truncation and phosphorylation are the most investigated. It is considered that PTMs of tau (except O-GlcNAcylation) interfere with\u00a0tau-microtubule (MT) binding, induce misfolding of tau, and thus contribute to tau aggregation. Therefore, targeting any of these PTMs has the potential to prevent tau aggregation and restore tau physiological functions.<\/p>\n The truncated tau has been shown to be a driving force of neurofibrillary degeneration. And truncated tau fragments containing repeat domains tend to aggregate and lose cytoskeletal MT-stabilizing properties. Hyperphosphorylation of the tau protein (primarily at Ser and Thr residues) affects its ability to bind tubulin and promote MT assembly, resulting in increased levels of unbound tau, thus increasing the possibility of tau-tau interactions\u00a0and polymerization.\u00a0Tau phosphorylation is strictly controlled by various protein kinases and phosphatases, among which glycogen synthase kinase 3\u03b2 (GSK-3\u03b2) and phosphatase 2A (PP2A) are two key enzymes involved in regulating tau phosphorylation state. The degree of tau phosphorylation during AD development reflects the abnormal activity of protein kinases and phosphatases. Tau phosphorylation is also regulated by O-GlcNAcylation. Tau undergoes PTMs\u00a0at Ser\/Thr residues by O-linked N-acetylglucosamine (O-GlcNAc), and thus the O-GlcNAcylation of tau protects it from phosphorylation.<\/p>\n![](\"https:\/\/www.creativebiomart.net\/alzheimacy\/wp-content\/themes\/alzheimacy\/images\/Targeting-Tau-Aggregation-1.jpg\")
\nFigure 1. Schematic diagram of tau aggregation process from monomers to NFTs. (Graham W V.; et al<\/em>. Update on Alzheimer\u2019s disease therapy and prevention strategies. Annual Review of Medicine<\/em>. 2017, 68(1): 413-430.)<\/p>\n