Advances in the Pathogenesis of Alzheimer's Disease: Focusing on Tau-Mediated Neurodegeneration

被引：54

作者：

Yale Duan

Suzhen Dong

Feng Gu

Yinghe Hu

Zheng Zhao

机构：

[1] Key Laboratory of Brain Functional Genomics, Ministry of Education, Shanghai Key Laboratory of Brain Functional Genomics, East China Normal University, Shanghai 200062

[2] Shanghai Engineering Research Center for Molecular Therapeutics and New Drug Development, East China Normal University

来源：

Translational Neurodegeneration | / 1卷 / 1期

基金：

中国国家自然科学基金;

关键词：

A-beta; Alzheimer's disease; Intraneuronal neurofibrillary tangles; Tau; Tau hyperphosphorylation; Tauopathy;

D O I：

10.1186/2047-9158-1-24

中图分类号：

学科分类号：

摘要：

In addition to senile plaques and cerebral amyloid angiopathy, the hyperphosphorylation of tau protein and formation of intraneuronal neurofibrillary tangles (NFTs) represents another neuropathological hallmark in AD brain. Tau is a microtubule-associated protein and localizes predominantly in the axons of neurons with the primary function in maintaining microtubules stability. When the balance between tau phosphorylation and dephosphorylation is changed in favor of the former, tau is hyperphosphorylated and the level of the free tau fractions elevated. The hyperphosphorylation of tau protein and formation of NFTs represent a characteristic neuropathological feature in AD brain. We have discussed the role of Aβ in AD in our previous review, this review focused on the recent advances in tau-mediated AD pathology, mainly including tau hyperphosphorylation, propagation of tau pathology and the relationship between tau and Aβ. © 2012 Duan et al.; licensee BioMed Central Ltd.

引用

共 68 条

[1]

Lee V.M., Goedert M., Trojanowski J.Q., Neurodegenerative tauopathies, Annu Rev Neurosci, 24, pp. 1121-1159, (2001)

[2]

Lee V.M.Y., Tauists and baptists United-Well Almost!, Science, 293, pp. 1446-1447, (2001)

[3]

Dong S.Z., Duan Y.L., Gu F., Hu Y.H., Zhao Z., Advances in the pathogenesis of Alzheimer's disease: a re-evaluation of amyloid cascade hypothesis, Translational Neurodegeneration, 1, (2012)

[4]

Goedert M., Spillantini M.G., Jakes R., Rutherford D., Crowther R.A., Multiple isoforms of human microtubule-associated protein tau: sequences and localization in neurofibrillary tangles of Alzheimer's disease, Neuron, 3, pp. 519-526, (1989)

[5]

Lee G., Cowan N., Kirschner M., The primary structure and heterogeneity of tau protein from mouse brain, Science, 239, pp. 285-288, (1988)

[6]

Hong M., Zhukareva V., Vogelsberg-Ragaglia V., Wszolek Z., Reed L., Miller B.I., Geschwind D.H., Bird T.D., McKeel D., Goate A., Et al., Mutation-specific functional impairments in distinct tau isoforms of hereditary FTDP-17, Science, 282, pp. 1914-1917, (1998)

[7]

Mazanetz M.P., Fischer P.M., Untangling tau hyperphosphorylation in drug design for neurodegenerative diseases, Nat Rev Drug Discov, 6, pp. 464-479, (2007)

[8]

Brion J.P., Octave J.N., Couck A.M., Distribution of the phosphorylated microtubule-associated protein tau in developing cortical neurons, Neuroscience, 63, pp. 895-909, (1994)

[9]

Yu Y., Run X., Liang Z., Li Y., Liu F., Liu Y., Iqbal K., Grundke-Iqbal I., Gong C.X., Developmental regulation of tau phosphorylation, tau kinases, and tau phosphatases, J Neurochem, 108, pp. 1480-1494, (2009)

[10]

Wang J.Z., Liu F., Microtubule-associated protein tau in development, degeneration and protection of neurons, Prog Neurobiol, 85, pp. 148-175, (2008)

← 1 2 3 4 5 6 7 →