Deposition of highly phosphorylated tau in the brain is the most significant neuropathological and biochemical characteristic of the group of neurodegenerative disorders termed the tauopathies. The discovery of tau fragments in these diseases suggests that tau cleavage and tau phosphorylation, both of which induce conformational changes in tau, could each have roles in disease pathogenesis. The identities of the proteases responsible for degrading tau, resulting in the appearance of truncated tau species in physiological and pathological conditions, are not known. Several fragments of tau are reported to have pro-aggregation properties, but the lack of disease-relevant cell models of tau aggregation has hampered investigation of the effects of tau aggregation on normal cellular functioning. In the present paper, we describe our findings of N-terminally truncated tau in the brain in a subgroup of the tauopathies in which tau isoforms containing four microtubule-binding domains predominate. We also discuss the evidence for the involvement of proteases in the generation of tau pathology in neurodegenerative disease, since these enzymes warrant further investigation as potential therapeutic targets in the tauopathies.
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Conference Article| July 26 2010
Tau cleavage and tau aggregation in neurodegenerative disease
Diane P. Hanger;
Diane P. Hanger 1
1MRC Centre for Neurodegeneration Research, Department of Neuroscience, King's College London, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, U.K.
1To whom correspondence should be addressed (email firstname.lastname@example.org).
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Publisher: Portland Press Ltd
Received: January 08 2010
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2010 Biochemical Society
Diane P. Hanger, Selina Wray; Tau cleavage and tau aggregation in neurodegenerative disease. Biochem Soc Trans 1 August 2010; 38 (4): 1016–1020. doi: https://doi.org/10.1042/BST0381016
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