Tau Protein Hyperphosphorylation and Aggregation in Alzheimer’s Disease and Other Tauopathies, and Possible Neuroprotective Strategies

Biomolecules - Tập 6 Số 1 - Trang 6
Goran Šimić1, Mirjana Babić Leko1, Selina Wray2, Charles R. Harrington3, Ivana Delalle4, Nataša Jovanov Milošević1, Danira Bažadona5, Luc Buée6, Rohan de Silva2, Giuseppe Di Giovanni7,8, Claude M. Wischik3, Patrick R. Hof9,10
1Department of Neuroscience, Croatian Institute for Brain Research, University of Zagreb School of Medicine, Zagreb 10000, Croatia
2Reta Lila Weston Institute and Department of Molecular Neuroscience, UCL Institute of Neurology, London WC1N 3BG, UK
3School of Medicine and Dentistry, University of Aberdeen, Aberdeen AB25 2ZD, UK
4Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston 02118, MA, USA
5Department of Neurology, University Hospital Center Zagreb, Zagreb 10000, Croatia
6Laboratory Alzheimer & Tauopathies, Université Lille and INSERM U1172, Jean-Pierre Aubert Research Centre, Lille 59045, France
7Department of Physiology and Biochemistry, Faculty of Medicine and Surgery, University of Malta, Msida MSD 2080, Malta
8School of Biosciences, Cardiff University, Cardiff, CF10 3AX, UK
9Fishberg Department of Neuroscience, Ronald M. Loeb Center for Alzheimer’s Disease, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
10Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA

Tóm tắt

Abnormal deposition of misprocessed and aggregated proteins is a common final pathway of most neurodegenerative diseases, including Alzheimer’s disease (AD). AD is characterized by the extraneuronal deposition of the amyloid β (Aβ) protein in the form of plaques and the intraneuronal aggregation of the microtubule-associated protein tau in the form of filaments. Based on the biochemically diverse range of pathological tau proteins, a number of approaches have been proposed to develop new potential therapeutics. Here we discuss some of the most promising ones: inhibition of tau phosphorylation, proteolysis and aggregation, promotion of intra- and extracellular tau clearance, and stabilization of microtubules. We also emphasize the need to achieve a full understanding of the biological roles and post-translational modifications of normal tau, as well as the molecular events responsible for selective neuronal vulnerability to tau pathology and its propagation. It is concluded that answering key questions on the relationship between Aβ and tau pathology should lead to a better understanding of the nature of secondary tauopathies, especially AD, and open new therapeutic targets and strategies.

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