Tau protein aggregation: Key features to improve drug discovery screening. Issue 5 (May 2022)

• Record Type: Journal Article
• Authors: Giovannini, Johanna; Smeralda, Willy; Jouanne, Marie; Sopkova-de Oliveira Santos, Jana; Catto, Marco; Voisin-Chiret, Anne Sophie
• Is Part Of: Drug discovery today. Volume 27:Issue 5(2022)
• Page Start: 1284
• Page End: 1297
• Publication Date: 2022-05
• Subjects: Tau protein -- Aggregation -- Therapeutic -- Drug design; Drugs -- Design -- Periodicals; Drugs -- Research -- Periodicals; 615.1
• DOI: 10.1016/j.drudis.2022.01.009
• Languages: English
• ISSNs: 1359-6446

Abstract

Graphical abstract: Highlights: Therapeutic management of tauopathies of major public health interest. Complexity of interaction with the tau protein related to its structural modification. Rational design of tau aggregation inhibitors. Development of tau aggregation inhibitors: from small molecules to antibodies. Abstract : Tauopathies are neurodegenerative disorders associated with the accumulation of abnormal tubulin associated unit (tau) protein in the brain. Tau pathologies include a broad spectrum of diseases, with Alzheimer's disease (AD) being the most common tauopathy. The pathophysiological mechanisms of AD are still only partially understood. As a consequence, attempts to establish therapeutic approaches have led to numerous clinical trial failures and, to date, no curative treatment is available for AD despite the considerable number of research programs. Therefore, over the past decade, the aggregation of the tau protein in AD has become a therapeutic target of interest. In this review, we gather in silico, in vitro, and in vivo methodologies that are relevant to assess compounds targeting tau aggregation, from early drug design to clinical trials.