An immunochemical study on tau glycation in paired helical filaments

Ko, Li Wen; Ko, Eric C.; Nacharaju, Parimala; Liu, Wan Kyng; Chang, E C; Kenessey, Ágnes; Yen, Shu Hui

doi:10.1016/s0006-8993(99)01415-8

Cited by 60 publications

(37 citation statements)

References 69 publications

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“…Their formation is thought to contribute to several pathophysiological conditions, including tissue damage after ischemia, aging, and the development of blindness and vascular diseases in diabetic patients (34,35). In AD, cross-linking by AGEs of lysine residues in the microtubule binding domain of tau results in the formation of detergent-insoluble and proteaseresistant aggregates such as NFT (2,3,36,37). In these, AGE determinants were localized in their fibrillar protein component, the tau filaments, by electron microscopy (38).…”

Section: Discussionmentioning

confidence: 99%

Role for glyoxalase I in Alzheimer's disease

Chen

Wollmer

Hoerndli

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

146

101

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P301L mutant tau transgenic mice develop neurofibrillary tangles, a histopathologic hallmark of Alzheimer's disease and frontotemporal dementia (FTDP-17). To identify differentially expressed genes and to gain insight into pathogenic mechanisms, we performed a stringent analysis of the microarray dataset obtained with RNA from whole brains of P301L mutant mice and identified a single up-regulated gene, glyoxalase I. This enzyme plays a critical role in the detoxification of dicarbonyl compounds and thereby reduces the formation of advanced glycation end products. In situ hybridization analysis revealed expression of glyoxalase I in all brain areas analyzed, both in transgenic and control mice. However, levels of glyoxalase I protein were significantly elevated in P301L brains, as shown by Western blot analysis and immunohistochemistry. Moreover, a glyoxalase I-specific antiserum revealed many intensely stained flame-shaped neurons in Alzheimer's disease brain compared with brains from nondemented controls. In addition, we examined a single nucleotide polymorphism predicting a nonconservative amino acid substitution at position 111 (E111A) in ethnically independent populations. We identified significant and consistent deviations from HardyWeinberg equilibrium, which points to the presence of selection forces. The E111A single nucleotide polymorphism was not associated with the risk for Alzheimer's disease in the overall population. Together, our data demonstrate the potential of transcriptomics applied to animal models of human diseases. They suggest a previously unidentified role for glyoxalase I in neurodegenerative disease. A lzheimer's disease (AD) and frontotemporal dementia are common forms of age-related dementing diseases. They are characterized by proteinaceous aggregates, which are resistant to proteolysis due to conformational changes and posttranslational modifications such as hyperphosphorylation and glycation (1-4). In AD, these aggregates are ␤-amyloid plaques and neurofibrillary tangles (NFT). NFT formation, in the absence of overt amyloid plaques, is found in a group of neurodegenerative diseases, including frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17) (5, 6). In affected cells, the microtubule-associated protein tau is abnormally phosphorylated and relocalized from axonal to somatodendritic compartments, where it accumulates in aggregates that eventually assemble into NFT (7). The identification of mutations in the tau gene in FTDP-17 established that dysfunction of tau in itself can lead to dementia (6).NFT formation has been reproduced in transgenic mice by expression of FTDP-17 mutant tau, both in neurons (8-12) and in glial cells (13)(14)(15). Moreover, intracerebral injection of ␤-amyloid fibrils caused significant increases of NFT in the amygdala of P301L (FTDP-17) mutant mice (16). A similar increase was achieved by crossing ␤-amyloid-producing amyloid precursor protein mutant mice with P301L mice (17).The pathologic similarities between the P301L transgenic ...

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Section: Discussionmentioning

confidence: 99%

Role for glyoxalase I in Alzheimer's disease

Chen

Wollmer

Hoerndli

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

146

101

View full text Add to dashboard Cite

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“…A central neuropathological feature of AD is the presence of neurofibrillary tangles, which are composed of hyperphosphorylated Tau protein [27]. Tau immunoreactivity (Tau-2) revealed the sharpest difference between nondemented and demented cases, as it was observed only in the neuropil of definite AD.…”

Section: Taumentioning

confidence: 99%

Immune reactive cells in senile plaques and cognitive decline in Alzheimer’s disease

Vehmas

Kawas

Stewart

et al. 2003

Neurobiology of Aging

207

134

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“…These dementia and movement disorders are characterized by formation of fibrillary inclusions containing hyperphosphorylated tau in neurons and glia [1,11]. In addition to phosphorylation, the inclusions have been reported to contain tau modified by ubiquitination, glycation, glycosylation, and nitration [1,7,9,14].…”

Section: Introductionmentioning

confidence: 99%

Increase in tau tyrosine phosphorylation correlates with the formation of tau aggregates

Vega

Cui

Propst

et al. 2005

Molecular Brain Research

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Tauopathies are neurodegenerative disorders characterized by aberrant intracellular aggregation of hyperphosphorylated tau. It has been shown that aggregated tau is phosphorylated at serine, threonine, and tyrosine residues. However, the occurrence of tyrosine phosphorylation on tau proteins at different states of tau aggregation has not been shown. In this report, we utilized the tauopathy mouse model JNPL3 that expresses human 0N4R tau isoform bearing the missense P301L mutation to study the occurrence of tau tyrosine phosphorylation in the course of the development of tau aggregation. These mice develop behavioral and motor deficits and form sarkosyl-insoluble hyperphosphorylated tau in an age-dependent manner. Mass spectrometry analyses of immunopurified brain tau proteins from JNPL3 and Alzheimer's disease affected individual uncovered novel tau tyrosine-phosphorylated sites. Further studies demonstrated that the abundance of tyrosine-phosphorylated tau increases in an age-dependent manner in JNPL3 mice. Tyrosine-phosphorylated tau was detected in both soluble and sarkosyl-insoluble preparations derived from brain and spinal cord, and localized in neurons containing aggregated tau. The phosphorylation of tyrosine residues in tau appeared to occur along with that of serine and threonine residues and was not detectable in non-transgenic littermates and transgenic mice expressing 0N4R wild-type human tau. The results suggest that tyrosine phosphorylation is as important as phosphorylation of other residues in tauopathy.

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An immunochemical study on tau glycation in paired helical filaments

Cited by 60 publications

References 69 publications

Role for glyoxalase I in Alzheimer's disease

Role for glyoxalase I in Alzheimer's disease

Immune reactive cells in senile plaques and cognitive decline in Alzheimer’s disease

Increase in tau tyrosine phosphorylation correlates with the formation of tau aggregates

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