Synergistic influence of phosphorylation and metal ions on tau oligomer formation and coaggregation with α-synuclein at the single molecule level

Nübling, Georg; Bader, Benedikt; Xiong, Chengjie; Hildebrandt, Jenna; Kretzschmar, Hans A.; Giese, Armin

doi:10.1186/1750-1326-7-35

Cited by 60 publications

(66 citation statements)

References 61 publications

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“…High concentrations of iron can increase oxidative stress and the toxicity of environmental or endogenous toxins, causing diseases such as AD and Parkinson's disease. At this stage, the oxidative injury and iron accumulation caused by HO-1 promote tauopathies, as previously reported [53,74,75].…”

Section: Discussionmentioning

confidence: 59%

Overexpression of Heme Oxygenase 1 Causes Cognitive Decline and Affects Pathways for Tauopathy in Mice

Wang

Yang

Peng

et al. 2014

JAD

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The stress protein heme oxygenase-1 (HO-1) is upregulated and co-localizes to pathological features, including tauopathies in the brains of individuals with Alzheimer's disease. However, the relationship between HO-1 and Alzheimer's disease remains unclear. In our previous research, the long-term overexpression of HO-1 was shown to promote tau aggregation by inducing tau phosphorylation in the mouse brain. In this study, we found that the long-term overexpression of HO-1 led to cognitive decline in transgenic mice, as determined by the water maze test, and that HO-1 can affect two pathways for tauopathy. Through one pathway, HO-1 promotes the expression of CDK5 by accumulating reactive oxygen species, which are produced by HO-1 downstream products of iron in neuro2a cell lines and mouse brain. Through the second pathway, HO-1 induces tau truncation at D421 in vivo and in vitro. Clearly, there is a HO-1-dependent mechanism responsible for tau protein phosphorylation and tau truncation in vivo and in vitro. Taken together, our results suggest that HO-1 plays an important role in the disease process of tauopathies in AD.

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Section: Discussionmentioning

confidence: 59%

Overexpression of Heme Oxygenase 1 Causes Cognitive Decline and Affects Pathways for Tauopathy in Mice

Wang

Yang

Peng

et al. 2014

JAD

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“…The oligomeric intermediates or amyloid forms of many proteins that are linked to human diseases demonstrate SDS resistance, including A␤ peptide, Tau, mammalian prion protein PrP, and proteins with polyglutamine stretches (55)(56)(57). Other functional amyloid proteins and yeast prion proteins also share this property (16, 58 -60).…”

Section: Discussionmentioning

confidence: 99%

Non-targeted Identification of Prions and Amyloid-forming Proteins from Yeast and Mammalian Cells

Kryndushkin¹,

Pripuzova

Burnett

et al. 2013

Journal of Biological Chemistry

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Background: Multiple protein amyloids can underlie both functional and pathological processes in various organisms. Results: The common properties of different amyloids enable their isolation and identification. Conclusion: A non-targeted proteomic approach can identify amyloid-forming and amyloid-associated proteins extracted directly from cells. Significance: Novel amyloid-associated proteins can be identified in less tractable organisms and model systems, requiring no special genetic tools.

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“…Using the fluorescent intensity distribution analysis technique (FIDA), Nübling and colleagues have shown that tau and αsyn can form co-oligomers and that co-aggregation happens even at nanomolar concentrations but only in the presence of a cationic aggregation inducer such as Al 3+ and Fe 3+ or DMSO [158]. Moreover, tau phosphorylation by GSK3β strongly enhanced the formation of mixed oligomers [158].…”

Section: Tau and α-Synuclein In Molecular Studiesmentioning

confidence: 99%

Alpha-synuclein and tau: teammates in neurodegeneration?

Moussaud

Jones

Moussaud-Lamodière

et al. 2014

Mol Neurodegeneration

226

195

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The accumulation of α-synuclein aggregates is the hallmark of Parkinson’s disease, and more generally of synucleinopathies. The accumulation of tau aggregates however is classically found in the brains of patients with dementia, and this type of neuropathological feature specifically defines the tauopathies. Nevertheless, in numerous cases α-synuclein positive inclusions are also described in tauopathies and vice versa, suggesting a co-existence or crosstalk of these proteinopathies. Interestingly, α-synuclein and tau share striking common characteristics suggesting that they may work in concord. Tau and α-synuclein are both partially unfolded proteins that can form toxic oligomers and abnormal intracellular aggregates under pathological conditions. Furthermore, mutations in either are responsible for severe dominant familial neurodegeneration. Moreover, tau and α-synuclein appear to promote the fibrillization and solubility of each other in vitro and in vivo. This suggests that interactions between tau and α-synuclein form a deleterious feed-forward loop essential for the development and spreading of neurodegeneration. Here, we review the recent literature with respect to elucidating the possible links between α-synuclein and tau.

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Synergistic influence of phosphorylation and metal ions on tau oligomer formation and coaggregation with α-synuclein at the single molecule level

Cited by 60 publications

References 61 publications

Overexpression of Heme Oxygenase 1 Causes Cognitive Decline and Affects Pathways for Tauopathy in Mice

Overexpression of Heme Oxygenase 1 Causes Cognitive Decline and Affects Pathways for Tauopathy in Mice

Non-targeted Identification of Prions and Amyloid-forming Proteins from Yeast and Mammalian Cells

Alpha-synuclein and tau: teammates in neurodegeneration?

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