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

Biomolecules

Goran Šimić⁶  Mirjana Babić Leko⁶  Selina Wray⁷  Charles Harrington²  Ivana Delalle¹  Nataᘚ Jovanov-Miloᘞvić⁶  Danira Ba𗺭ona³  Luc Buພ⁴  Rohan de Silva⁷  Giuseppe Di Giovanni⁸  Claude Wischik²  Patrick R. Hof⁵ 

[1] Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston 02118, MA, USA;School of Medicine and Dentistry, University of Aberdeen, Aberdeen AB25 2ZD, UK;Department of Neurology, University Hospital Center Zagreb, Zagreb 10000, Croatia;Laboratory Alzheimer & Tauopathies, Université Lille and INSERM U1172, Jean-Pierre Aubert Research Centre, Lille 59045, France;Fishberg Department of Neuroscience, Ronald M. Loeb Center for Alzheimer’s Disease, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA;Department of Neuroscience, Croatian Institute for Brain Research, University of Zagreb School of Medicine, Zagreb 10000, Croatia;Reta Lila Weston Institute and Department of Molecular Neuroscience, UCL Institute of Neurology, London WC1N 3BG, UK;Department of Physiology and Biochemistry, Faculty of Medicine and Surgery, University of Malta, Msida, MSD 2080, Malta;

关键词: Alzheimer’s disease;    amyloid β;    neurofibrillary degeneration;    microtubules;    neuropathology;    phosphorylation;    protein aggregation;    protein oligomerization;    tauopathies;    tau protein;   

DOI  :  10.3390/biom6010006

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2016 by the authors; licensee MDPI, Basel, Switzerland.