NEURODEGENERATIVE DISEASES AND TAU: PATHOLOGICAL EVENTS AND MOLECULAR TARGETS

Abstract

The neuronal protein tau, and the related neurodegenerative diseases named tauopathies, are thoroughly described here. Tau is characterized in terms of its disorganized structure, of its isoforms, and of its structural domains. Tau mutations, and their consequences on the functions of tau (detachment from microtubules, aggregation into soluble oligomers and insoluble aggregates), are mentioned to introduce a set of ≈30 tauopathies. The pattern of post-translational modifications of tau is described, to explain its impact – when disregulated – on the folding and mislocalization of tau, followed by its aggregation. In details, tau hyper-phosphorylation (negative regulator, to be inhibited), N-Acetylglucosamine glycosylation and pT231-P232 cis-trans isomerization (positive regulator, to be stimulated) are described in terms of their connection to tau biochemical abnormalities, and of their exploitation as tauopathy-directed molecular targets.