Pathological truncations of human brain proteins represent the common feature of many neurodegenerative disorders including AD (Alzheimer's disease), Parkinson's disease and Huntington's disease. Protein truncations significantly change the structure and function of these proteins and thus can engender their pathological metamorphosis. We have shown previously that truncated forms of tau protein are contained in the core of the paired helical filaments that represent the main constituent of neurofibrillary pathology. Recently, we have identified truncated tau species of a different molecular signature. We have found that tau truncation is not produced by a random process, but rather by highly specific proteolytic cleavage and/or non-enzymatic fragmentation. In order to characterize the pathophysiology of AD-specific truncated tau species, we have used a transgenic rat model for AD expressing human truncated tau. Expression of the tau protein induces the formation of novel truncated tau species that originate from both transgenic human tau and endogenous rat tau proteins. Moreover, these truncated tau proteins are found exclusively in the misfolded fraction of tau, suggesting that they actively participate in the tau misfolding process. These findings corroborate further the idea that the appearance of truncated tau species starts a self-perpetuating cycle of further tau protein truncation leading to and accelerating tau misfolding and formation of neurofibrillary pathology.
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August 2012
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Conference Article|
July 20 2012
The self-perpetuating tau truncation circle
Norbert Zilka;
Norbert Zilka
1
1Institute of Neuroimmunology, Slovak Academy of Sciences, Dubravska cesta 9, Bratislava 84510, Slovak Republic, and Axon Neuroscience GmbH, Rennweg 95b, 1030 Vienna, Austria
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Branislav Kovacech;
Branislav Kovacech
1
1Institute of Neuroimmunology, Slovak Academy of Sciences, Dubravska cesta 9, Bratislava 84510, Slovak Republic, and Axon Neuroscience GmbH, Rennweg 95b, 1030 Vienna, Austria
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Peter Barath;
Peter Barath
1
1Institute of Neuroimmunology, Slovak Academy of Sciences, Dubravska cesta 9, Bratislava 84510, Slovak Republic, and Axon Neuroscience GmbH, Rennweg 95b, 1030 Vienna, Austria
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Eva Kontsekova;
Eva Kontsekova
1Institute of Neuroimmunology, Slovak Academy of Sciences, Dubravska cesta 9, Bratislava 84510, Slovak Republic, and Axon Neuroscience GmbH, Rennweg 95b, 1030 Vienna, Austria
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Michal Novák
Michal Novák
2
1Institute of Neuroimmunology, Slovak Academy of Sciences, Dubravska cesta 9, Bratislava 84510, Slovak Republic, and Axon Neuroscience GmbH, Rennweg 95b, 1030 Vienna, Austria
2To whom correspondence should be addressed (emailmichal.novak@savba.sk).
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Publisher: Portland Press Ltd
Received:
January 18 2012
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2012 Biochemical Society
2012
Biochem Soc Trans (2012) 40 (4): 681–686.
Article history
Received:
January 18 2012
Citation
Norbert Zilka, Branislav Kovacech, Peter Barath, Eva Kontsekova, Michal Novák; The self-perpetuating tau truncation circle. Biochem Soc Trans 1 August 2012; 40 (4): 681–686. doi: https://doi.org/10.1042/BST20120015
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