Tau Protein Hyperphosphorylation and Aggregation in Alzheimer’s Disease and Other Tauopathies, and Possible Neuroprotective Strategies
Top Cited Papers
Open Access
- 5 January 2016
- journal article
- review article
- Published by MDPI AG in Biomolecules
- Vol. 6 (1), 6
- https://doi.org/10.3390/biom6010006
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.This publication has 194 references indexed in Scilit:
- Human fetal tau protein isoform: Possibilities for Alzheimer's disease treatmentThe International Journal of Biochemistry & Cell Biology, 2012
- Propagation of Tau Pathology in a Model of Early Alzheimer's DiseaseNeuron, 2012
- The Many Faces of TauNeuron, 2011
- Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's diseaseNature Genetics, 2011
- Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer's diseaseNature Genetics, 2011
- Nuclear Tau, a Key Player in Neuronal DNA ProtectionJournal of Biological Chemistry, 2011
- Propagation of Tau Misfolding from the Outside to the Inside of a CellPublished by Elsevier BV ,2009
- An inhibitor of tau hyperphosphorylation prevents severe motor impairments in tau transgenic miceProceedings of the National Academy of Sciences of the United States of America, 2006
- Neuropathological stageing of Alzheimer-related changesActa Neuropathologica, 1991
- Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's diseaseNature, 1991