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Advances in Alzheimer's Research
VOLUME: 1
Editor(s): Debomoy K. Lahiri
eISBN: 978-1-60805-495-4   ISBN: 978-1-60805-714-6   ISSN :2214-4358
Chapter PDF Price: US $30
   



Tau-Induced Neurodegeneration in Alzheimer Disease and Related Tauopathies

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Author(s): Alejandra del C. Alonso, Bin Li, Inge Grundke-Iqbal and Khalid Iqbal
Chapter DOI: 10.2174/9781608054954113010013
Page: 234-259 (26)

Abstract:
The accumulation of hyperphosphorylated tau is a common feature of several dementias. Tau is one of the brain microtubule–associated proteins. Here, we discuss tau’s function in microtubule assembly and stabilization with regards to tau’s interactions with other proteins, membranes, and DNA. We describe and analyze important posttranslational modifications: hyperphosphorylation, glycosylation, ubiquitination, glycation, polyamination, nitration, acetylation, methylation, and truncation. We discuss how these post-translational modifications can alter tau’s biological functions and what is known about tau self-assembly, and we propose a mechanism of tau polymerization. We analyze the impact of natural mutations on tau that cause fronto-temporal dementia associated with chromosome 17 (FTDP-1 7). Finally, we consider whether tau accumulation or its conformational change is related to tau-induced neurodegeneration, and we propose a mechanism of neurodegeneration.
Keywords:
Tau, phosphorylation, microtubules, tubulin, neurodegeneration, Alzheimer, paired helical filaments, protein aggregation, kinases, phosphatases, frontotemporal dementia, posttranslational modifications, MAPs, actin, glycosilation, ubiquitination, truncation, tau mutations, protein conformation, misfolded proteins.
Affiliation:
Department of Biology and Center for Developmental Neuroscience and Developmental Disabilities, College of Staten Island, The City University of New York, Staten Island, NY 10314, USA.