Tau Conformation as a Target for Disease-Modifying Therapy: The Role of Truncation

Tau protein plays a major role in the pathogenesis of Alzheimer's disease. Despite many decades of intensive research, the cause of the conformational switch that leads to the remodeling of the highly flexible conformational ensemble of intrinsically disordered protein tau into insoluble filame...

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Bibliographic Details
Published inJournal of Alzheimer's disease Vol. 64; no. s1; p. S535
Main Authors Novak, Petr, Cehlar, Ondrej, Skrabana, Rostislav, Novak, Michal
Format Journal Article
LanguageEnglish
Published Netherlands 01.01.2018
Subjects
Animals
Humans
Protein Conformation
tau Proteins - metabolism
Tauopathies - metabolism
Tauopathies - therapy
Aggregation
conformational ensemble
Alzheimer’s disease
tau protein
truncation
immunotherapy
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Summary:Tau protein plays a major role in the pathogenesis of Alzheimer's disease. Despite many decades of intensive research, the cause of the conformational switch that leads to the remodeling of the highly flexible conformational ensemble of intrinsically disordered protein tau into insoluble filaments is still elusive. We show here that truncation of tau may play a causative role in this conformational change, as evidenced by results obtained from in vitro experiments and from transgenic animal models. This conformational change is a common denominator of pathological tau protein assemblies, and a salient drug target. The long-running research of truncated tau has led to the generation of the first active tau vaccine that has entered clinical trials.
ISSN:1875-8908
DOI:10.3233/JAD-179942