Structure and Pathology of Tau Protein in Alzheimer Disease

Abstract

Alzheimer's disease (AD) is the most common type of dementia. In connection with the global trend of prolonging human life and the increasing number of elderly in the population, the AD becomes one of the most serious health and socioeconomic problems of the present. Tau protein promotes assembly and stabilizes microtubules, which contributes to the proper function of neuron. Alterations in the amount or the structure of tau protein can affect its role as a stabilizer of microtubules as well as some of the processes in which it is implicated. The molecular mechanisms governing tau aggregation are mainly represented by several posttranslational modifications that alter its structure and conformational state. Hence, abnormal phosphorylation and truncation of tau protein have gained attention as key mechanisms that become tau protein in a pathological entity. Evidences about the clinicopathological significance of phosphorylated and truncated tau have been documented during the progression of AD as well as their capacity to exert cytotoxicity when expressed in cell and animal models. This paper describes the normal structure and function of tau protein and its major alterations during its pathological aggregation in AD.

Protein Oxidation in Aging: Does It Play a Role in Aging Progression?

“…Tau, the term derived from ''tubulin associated unit,'' is a protein that is highly expressed in the human brain and which functions in binding and stabilization of microtubules (91,107). Phosphorylation ensures the biological activity of tau.…”

“…Thus, NFTs consist of aggregated and hyperphosphorylated tau proteins, displaying one of the most important markers for AD. Since microtubules are not able to function correctly, aggregation of tau finally leads to an impaired neuronal transport (17,91).…”

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“…However, they all exhibit a similar structure, differing only in the number of microtubule-binding domains, as well as in the number of N-terminal inserts. In general, tau proteins consist of a C-terminal region that encompasses a proline-rich domain which is capable of interacting with microtubules [37]. On the other hand, the N-terminal domain consists of repeats of amino acids which do not bind to tubulin.…”

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“…The tau protein is a microtubule associating protein (MAP) stimulating tubulin assembly into microtubules in the brain (8) and a normal phosphorlyation level is required for its optimal function, however the hyperphosphorylation of the same results into loss of its biological activity (9).…”