Post-translational modifications of tau protein in Alzheimer's disease

被引：436

作者：

Gong, CX ^{[1
]}

Liu, F ^{[1
]}

Grundke-Iqbal, I ^{[1
]}

Iqbal, K ^{[1
]}

机构：

[1] New York State Inst Basic Res Dev Disabil, Dept Neurochem, Staten Isl, NY 10314 USA

来源：

JOURNAL OF NEURAL TRANSMISSION | 2005年 / 112卷 / 06期

关键词：

Alzheimer's disease; tau; post-translational modifications; neurofibrillary degeneration; hyperphosphorylation; glycosylation; glycation; polyamination; nitration; ubiquitination; proteolysis; cerebrospinal fluid; biomarker;

D O I：

10.1007/s00702-004-0221-0

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Microtubule-associated protein tau undergoes several post-translational modifications and aggregates into paired helical filaments (PHFs) in Alzheimer's disease (AD) and other tauopathies. These modifications of tau include hyperphosphorylation, glycosylation, ubiquitination, glycation, polyamination, nitration, and proteolysis. Hyperphosphorylation and glycosylation are crucial to the molecular pathogenesis of neurofibrillary degeneration of AD. The others appear to represent failed mechanisms for neurons to remove damaged, misfolded, and aggregated proteins. This review summarizes the abnormal posttranslational modifications of tau and discusses the pathophysiological relevance of hyperphosphorylation and glycosylation of tau. Total tau and phosphorylated tau levels in cerebrospinal fluid as a diagnostic biomarkers are also reviewed. Analyses of the current advances in tau modifications suggest that intervention addressing these abnormalities may offer promising therapeutic opportunities to prevent and treat neurofibrillary degeneration of AD and other tauopathies.

引用

页码：813 / 838

页数：26

共 197 条

[1] Abnormal phosphorylation of tan and the mechanism of Alzheimer neurofibrillary degeneration: Sequestration of microtubule-associated proteins 1 and 2 and the disassembly of microtubules by the abnormal tau [J].

Alonso, AD ;

GrundkeIqbal, I ;

Barra, HS ;

Iqbal, K .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (01) :298-303

[2] Alzheimer's disease hyperphosphorylated tau sequesters normal tau into tangles of filaments and disassembles microtubules [J].

Alonso, AD ;

GrundkeIqbal, I ;

Iqbal, K .

NATURE MEDICINE, 1996, 2 (07) :783-787

[3]

Alonso AD, 2001, J BIOL CHEM, V276, P37967

[4] ROLE OF ABNORMALLY PHOSPHORYLATED TAN IN THE BREAKDOWN OF MICROTUBULES IN ALZHEIMER-DISEASE [J].

ALONSO, AD ;

ZAIDI, T ;

GRUNDKEIQBAL, I ;

IQBAL, K .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (12) :5562-5566

[5] Promotion of hyperphosphorylation by frontotemporal dementia tau mutations [J].

Alonso, AD ;

Mederlyova, A ;

Novak, M ;

Grundke-Iqbal, I ;

Iqbal, K .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (33) :34873-34881

[6] Hyperphosphorylation induces self-assembly of τ into tangles of paired helical filaments/straight filaments [J].

Alonso, AD ;

Zaidi, T ;

Novak, M ;

Grundke-Iqbal, I ;

Iqbal, K .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (12) :6923-6928

[7] RELATIVE EXON AFFINITIES AND SUBOPTIMAL SPLICE-SITE SIGNALS LEAD TO NON-EQUIVALENCE OF 2 CASSETTE EXON [J].

ANDREADIS, A ;

BRODERICK, JA ;

KOSIK, KS .

NUCLEIC ACIDS RESEARCH, 1995, 23 (17) :3585-3593

[8] STRUCTURE AND NOVEL EXONS OF THE HUMAN-TAU GENE [J].

ANDREADIS, A ;

BROWN, WM ;

KOSIK, KS .

BIOCHEMISTRY, 1992, 31 (43) :10626-10633

[9] Cerebrospinal fluid tau and Aβ42 as predictors of development of Alzheimer's disease in patients with mild cognitive impairment [J].

Andreasen, N ;

Minthon, L ;

Vanmechelen, E ;

Vanderstichele, H ;

Davidsson, P ;

Winblad, B ;

Blennow, K .

NEUROSCIENCE LETTERS, 1999, 273 (01) :5-8

[10] Cerebrospinal fluid tau protein as a biochemical marker for Alzheimer's disease:: a community based follow up study [J].

Andreasen, N ;

Vanmechelen, E ;

Van de Voorde, A ;

Davidsson, P ;

Hesse, C ;

Tarvonen, S ;

Räihä, I ;

Sourander, L ;

Winblad, B ;

Blennow, K .

JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, 1998, 64 (03) :298-305

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