Advances in Alzheimer's Research

Advances in Alzheimer's Research

Alzheimer’s disease (AD) is currently recognized as an untreatable, progressive, degenerative and terminal disease that is globally afflicting an estimated 36 million people and this number is growi
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Tau-Induced Neurodegeneration in Alzheimer Disease and Related Tauopathies

Pp. 234-259 (26)

Alejandra del C. Alonso, Bin Li, Inge Grundke-Iqbal and Khalid Iqbal

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.