title: Tau Protein Hyperphosphorylation and Aggregation in Alzheimer's Disease and Other Tauopathies, and Possible Neuroprotective Strategies.
abstract: 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.
authors.affiliation: Department of Neuroscience, Croatian Institute for Brain Research, University of Zagreb School of Medicine, Zagreb 10000, Croatia. gsimic@hiim.hr.
authors.forename: Goran
authors.initials: G
authors.lastname: Šimić
authors.affiliation: Department of Neuroscience, Croatian Institute for Brain Research, University of Zagreb School of Medicine, Zagreb 10000, Croatia. mbabic@hiim.hr.
authors.forename: Mirjana
authors.initials: M
authors.lastname: Babić Leko
authors.affiliation: Reta Lila Weston Institute and Department of Molecular Neuroscience, UCL Institute of Neurology, London WC1N 3BG, UK. selina.wray@ucl.ac.uk.
authors.forename: Selina
authors.initials: S
authors.lastname: Wray
authors.affiliation: School of Medicine and Dentistry, University of Aberdeen, Aberdeen AB25 2ZD, UK. c.harrington@abdn.ac.uk.
authors.forename: Charles
authors.initials: C
authors.lastname: Harrington
authors.affiliation: Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston 02118, MA, USA. idelalle@bu.edu.
authors.forename: Ivana
authors.initials: I
authors.lastname: Delalle
authors.affiliation: Department of Neuroscience, Croatian Institute for Brain Research, University of Zagreb School of Medicine, Zagreb 10000, Croatia. njovanov@hiim.hr.
authors.forename: Nataša
authors.initials: N
authors.lastname: Jovanov-Milošević
authors.affiliation: Department of Neurology, University Hospital Center Zagreb, Zagreb 10000, Croatia. b.danira@gmail.com.
authors.forename: Danira
authors.initials: D
authors.lastname: Bažadona
authors.affiliation: Laboratory Alzheimer & Tauopathies, Université Lille and INSERM U1172, Jean-Pierre Aubert Research Centre, Lille 59045, France. luc.buee@inserm.fr.
authors.forename: Luc
authors.initials: L
authors.lastname: Buée
authors.affiliation: Reta Lila Weston Institute and Department of Molecular Neuroscience, UCL Institute of Neurology, London WC1N 3BG, UK. r.desilva@ucl.ac.uk.
authors.forename: Rohan
authors.initials: R
authors.lastname: de Silva
authors.affiliation: Department of Physiology and Biochemistry, Faculty of Medicine and Surgery, University of Malta, Msida, MSD 2080, Malta. giuseppe.digiovanni@um.edu.mt.|School of Biosciences, Cardiff University, Cardiff CF10 3AX, UK. giuseppe.digiovanni@um.edu.mt.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Di Giovanni
authors.affiliation: School of Medicine and Dentistry, University of Aberdeen, Aberdeen AB25 2ZD, UK. cmw@taurx.com.
authors.forename: Claude
authors.initials: C
authors.lastname: Wischik
authors.affiliation: Fishberg Department of Neuroscience, Ronald M. Loeb Center for Alzheimer's Disease, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. patrick.hof@mssm.edu.|Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. patrick.hof@mssm.edu.
authors.forename: Patrick R
authors.initials: PR
authors.lastname: Hof
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D006801:Humans; D016874:Neurofibrillary Tangles; D018696:Neuroprotective Agents / Q000627:therapeutic use; D010766:Phosphorylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D024801:Tauopathies / Q000188:drug therapy* / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; C054369:MAPT protein, human; D018696:Neuroprotective Agents; D016875:tau Proteins
keywords: Alzheimer’s disease; amyloid β; microtubules; neurofibrillary degeneration; neuropathology; phosphorylation; protein aggregation; protein oligomerization; tau protein; tauopathies