Abstract
Mainstream thinking is dominated by the notion that the aggregation of specific proteins within neurons, and their subsequent formation into cytoplasmic and extracellular lesions, directly elicits neuronal dysfunction and death. Current dogma, for example, maintains that phosphorylated tau protein, the major component of neurofibrillary tangles, is a central mediator of disease pathogenesis. In this article, we challenge this classic notion by proposing that tau phosphorylation represents a compensatory response mounted by neurons against oxidative stress that serves a protective function. This concept provides a better understanding of the mechanisms underlying disease pathophysiology and also provides a window for therapeutic intervention.
Keywords: Alzheimer disease, neuron, oxidative stress, phosphorylation, tau, NFT, PHF, pathogenic factor, microtubules, Ser-396/Ser-404, phosphorylated tau, AGEs, JNK/SAPK
Current Alzheimer Research
Title: A Novel Perspective on Tau in Alzheimers Disease
Volume: 8 Issue: 6
Author(s): D. J. Bonda, R. J. Castellani, X. Zhu, A. Nunomura, H.-g. Lee, G. Perry and M. A. Smith
Affiliation:
Keywords: Alzheimer disease, neuron, oxidative stress, phosphorylation, tau, NFT, PHF, pathogenic factor, microtubules, Ser-396/Ser-404, phosphorylated tau, AGEs, JNK/SAPK
Abstract: Mainstream thinking is dominated by the notion that the aggregation of specific proteins within neurons, and their subsequent formation into cytoplasmic and extracellular lesions, directly elicits neuronal dysfunction and death. Current dogma, for example, maintains that phosphorylated tau protein, the major component of neurofibrillary tangles, is a central mediator of disease pathogenesis. In this article, we challenge this classic notion by proposing that tau phosphorylation represents a compensatory response mounted by neurons against oxidative stress that serves a protective function. This concept provides a better understanding of the mechanisms underlying disease pathophysiology and also provides a window for therapeutic intervention.
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Cite this article as:
J. Bonda D., J. Castellani R., Zhu X., Nunomura A., Lee H.-g., Perry G. and A. Smith M., A Novel Perspective on Tau in Alzheimers Disease, Current Alzheimer Research 2011; 8 (6) . https://dx.doi.org/10.2174/156720511796717131
DOI https://dx.doi.org/10.2174/156720511796717131 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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