Acknowledgments This work was supported by The Croatian Science Foundation grant No. IP-2014-09-9730 (“Tau protein hyperphosphorylation, aggregation, and trans-synaptic transfer in Alzheimer’s disease: cerebrospinal fluid analysis and assessment of potential neuroprotective compounds”) and European Cooperation in Science and Technology (COST) Action CM1103 (“Stucture-based drug design for diagnosis and treatment of neurological diseases: dissecting and modulating complex function in the monoaminergic systems of the brain”). PRH is supported in part by NIH grant P50 AG005138. We also thank Mate Babić for help in preparation of schematics.Peer reviewedPublisher PD

Babić Leko, Mirjana

Bažadona, Danira

Buée, Luc

de Silva, Rohan

Delalle, Ivana

Giovanni, Giuseppe Di

Harrington, Charles

Hof, Patrick R.

Jovanov-Milošević, Nataša

Wischik, Claude

Wray, Selina

Šimić, Goran

Biomolecules

English

PubMed

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

Di Giovanni, Giuseppe

University of Zagreb Medical School Repository

Tau protein hyperphosphorylation and aggregation in Alzheimer's disease and other tauopathies, and possible neuroprotective strategies

Acknowledgments This work was supported by The Croatian Science Foundation grant No. IP-2014-09-9730 (“Tau protein hyperphosphorylation, aggregation, and trans-synaptic transfer in Alzheimer’s disease: cerebrospinal fluid analysis and assessment of potential neuroprotective compounds”) and European Cooperation in Science and Technology (COST) Action CM1103 (“Stucture-based drug design for diagnosis and treatment of neurological diseases: dissecting and modulating complex function in the monoaminergic systems of the brain”). PRH is supported in part by NIH grant P50 AG005138. We also thank Mate Babić for help in preparation of schematics.Peer reviewe

Aberdeen University Research

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

Goran Šimić

Mirjana Babić Leko

Selina Wray

Charles Harrington

Ivana Delalle

Nataša Jovanov-Milošević

Danira Bažadona

Luc Buée

Rohan de Silva

Giuseppe Di Giovanni

Claude Wischik

Patrick Hof

Crossref

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.peer-reviewe

Simic, Goran

Babic Leko, Mirjana

Harrington, Charles R.

Jovanov-Milosevic, Natasa

Bazadona, Danira

Buee, Luc

De Silva, Rohan

Wischik, Claude M.

OAR@UM

University of Zagreb Repository

Šimić, G

Babić Leko, M

Wray, S

Harrington, C

Delalle, I

Jovanov-Milošević, N

Bažadona, D

Buée, L

De Silva, R

Di Giovanni, G

Wischik, C

Hof, PR

UCL Discovery

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

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

Patrick R. Hof

Directory of Open Access Journals

Rohan De Silva

Multidisciplinary Digital Publishing Institute

https://www.um.edu.mt/library/oar//bitstream/123456789/22587/3/biomolecules-06-00006-v2.pdf

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

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