Glyceraldehyde-3-phosphate Dehydrogenase Aggregates Accelerate Amyloid-β Amyloidogenesis in Alzheimer Disease

Itakura, Masanori; Nakajima, Hidemitsu; Kubo, Taeko; Semi, Yuko; Kume, Satoshi; Higashida, Shusaku; Kaneshige, Akihiro; Kuwamura, Mitsuru; Harada, Naoki; Kita, Akinori; Azuma, Yasutaka; Yamaji, Ryoichi; Inui, Takashi; Takeuchi, Tadayoshi

doi:10.1074/jbc.m115.669291

Cited by 67 publications

(40 citation statements)

References 65 publications

(100 reference statements)

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“…ThT fluorescence intensities, an indicator of fibre formation ability, were lowest for Aβ1–28 and Aβ11–42, intermediate for Aβ1–36 and Aβ17–42 and strongest for Aβ1–40 and Aβ1–42. These results are in accordance with those of other studies .…”

Section: Resultssupporting

confidence: 94%

Dissecting the behaviour of β‐amyloid peptide variants during oligomerization and fibrillation

Shi

Zhang

Liu

2017

Journal of Peptide Science

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The oligomerization and fibrillation of β-amyloid (Aβ) peptides are important events in the pathogenesis of Alzheimer's disease. However, the motifs within the Aβ sequence that contribute to oligomerization and fibrillation and the complex interplay among these short motifs are unclear. In this study, the oligomerization and fibrillation abilities of the Aβ variants Aβ1-28, Aβ1-36, Aβ11-42, Aβ17-42, Aβ1-40 and Aβ1-42 were examined by thioflavin T fluorescence, western blotting and transmission electron microscopy. Compared with two C-terminal-truncated peptides (i.e. Aβ1-28 and Aβ1-36), Aβ11-42, Aβ17-42 and Aβ1-42 had stronger abilities to form oligomers. This indicated that amino acids 37-42 strengthen the β-hairpin structure of Aβ. Both Aβ1-42 and Aβ1-40 could form fibres, but Aβ17-42 formed irregular fibres, suggesting that amino acids 1-17 were essential for Aβ fibre formation. Aβ1-28 and Aβ1-36 exhibited weak oligomerization and fibrillation, implying that they formed an unstable β-hairpin structure owing to the incomplete C-terminal region. Intermediate peptides were likely to form a stable structure, consistent with previous results. This work explains the roles and interplay among motifs within Aβ during oligomerization and fibrillation. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.

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Section: Resultssupporting

confidence: 94%

Dissecting the behaviour of β‐amyloid peptide variants during oligomerization and fibrillation

Shi

Zhang

Liu

2017

Journal of Peptide Science

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“…that are naturally resistant to NS35 which suggest that GAPDH has a protective role against NS in this parasite. In contrast GAPDH can trigger cell death in oxidatively- and nitrosatively-stressed mammalian cells363738. GAPDH expression is upregulated in trophozoites exposed to NS5 however we have no knowledge about the beneficial or detrimental effect that GAPDH has on E. histolytica exposed to NS.…”

Section: Resultsmentioning

confidence: 98%

N-acetyl ornithine deacetylase is a moonlighting protein and is involved in the adaptation of Entamoeba histolytica to nitrosative stress

Shahi

Trebicz-Geffen

Nagaraja

et al. 2016

Sci Rep

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Adaptation of the Entamoeba histolytica parasite to toxic levels of nitric oxide (NO) that are produced by phagocytes may be essential for the establishment of chronic amebiasis and the parasite’s survival in its host. In order to obtain insight into the mechanism of E. histolytica’s adaptation to NO, E. histolytica trophozoites were progressively adapted to increasing concentrations of the NO donor drug, S-nitrosoglutathione (GSNO) up to a concentration of 110 μM. The transcriptome of NO adapted trophozoites (NAT) was investigated by RNA sequencing (RNA-seq). N-acetyl ornithine deacetylase (NAOD) was among the 208 genes that were upregulated in NAT. NAOD catalyzes the deacetylation of N-acetyl-L-ornithine to yield ornithine and acetate. Here, we report that NAOD contributes to the better adaptation of the parasite to nitrosative stress (NS) and that this function does not depend on NAOD catalytic activity. We also demonstrated that glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is detrimental to E. histolytica exposed to NS and that this detrimental effect is neutralized by NAOD or by a catalytically inactive NAOD (mNAOD). These results establish NAOD as a moonlighting protein, and highlight the unexpected role of this metabolic enzyme in the adaptation of the parasite to NS.

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“…In native PAGE experiments, precursor protein signals were shifted to a high–molecular weight complex in the range of 700 kDa that copurified with Aβ42. Of interest, recent results showing negative consequences of coaggregation between cytosolic enzymes and Aβ peptides support this AD‑specific pathological mechanism (Itakura et al , 2015). Our work therefore adds an important aspect concerning the deleterious consequences of coaggregation processes during the etiology of neurodegenerative diseases.…”

Section: Discussionmentioning

confidence: 90%

Amyloid β-peptides interfere with mitochondrial preprotein import competence by a coaggregation process

Cenini

Rüb

Bruderek

et al. 2016

MBoC

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Glyceraldehyde-3-phosphate Dehydrogenase Aggregates Accelerate Amyloid-β Amyloidogenesis in Alzheimer Disease

Cited by 67 publications

References 65 publications

Dissecting the behaviour of β‐amyloid peptide variants during oligomerization and fibrillation

Dissecting the behaviour of β‐amyloid peptide variants during oligomerization and fibrillation

N-acetyl ornithine deacetylase is a moonlighting protein and is involved in the adaptation of Entamoeba histolytica to nitrosative stress

Amyloid β-peptides interfere with mitochondrial preprotein import competence by a coaggregation process

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