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Updated: Aug 17, 2026

Rapid Generation of Amyloid from Native Proteins In vitro
Published on: December 5, 2013
Amyloid-beta fibril formation is not necessarily required for microglial activation by the peptides
Sadayuki Hashioka1, Akira Monji, Tadashi Ueda
1Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Abstract:
There is increasing evidence that microglial activation has pathogenic influence on Alzheimer's disease. According to in vitro studies, microglia activated by amyloid-beta (Abeta) peptides have been reported to damage or kill neurons by the release of neurotoxic molecules such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta, nitric oxide or reactive oxygen species. Although the relationship between the aggregational state of Abeta peptides and their neurotoxic activities has been well investigated, little is known about the relationship between the aggregational state of Abeta peptides and their ability to induce microglial activation. In the present study, we thus performed both structural and biochemical studies to clarify the relationship between the aggregational state of Abeta peptides and their ability to activate microglia. Our results have shown that, in the presence of interferon-gamma, the Abeta25-35(M(35)Nle) peptide had almost the same potency of activating microglia and producing TNF-alpha as the Abeta25-35 peptide on both protein and mRNA levels, in spite of the fact that former peptide represented much less amyloid fibril formation than the latter in a thioflavine-T fluorometric assay. These results suggest that Abeta fibril formation is not necessarily required for microglial activation by the peptides.
Insights
Microglial activation plays a role in Alzheimer's disease. This study shows amyloid-beta (Abeta) fibril formation is not essential for activating microglia or producing tumor necrosis factor-alpha (TNF-alpha).
Area of Science:
- Neuroscience
- Immunology
- Biochemistry
Background:
- Microglial activation by amyloid-beta (Abeta) peptides contributes to Alzheimer's disease pathogenesis.
- Activated microglia release neurotoxic molecules, damaging neurons.
- The link between Abeta peptide aggregation state and microglial activation is poorly understood.
Purpose of the Study:
- To investigate the relationship between the aggregation state of Abeta peptides and their ability to activate microglia.
- To clarify how Abeta peptide structure influences microglial activation and neuroinflammation.
Main Methods:
- Structural and biochemical studies were performed on Abeta peptides.
- Microglial activation and TNF-alpha production were assessed in the presence of interferon-gamma.
- Thioflavine-T fluorometric assay was used to measure amyloid fibril formation.
Main Results:
- Abeta25-35(M(35)Nle) peptide showed similar potency in activating microglia and producing TNF-alpha as Abeta25-35 peptide.
- This occurred despite significantly less amyloid fibril formation by Abeta25-35(M(35)Nle) compared to Abeta25-35.
- Results were observed at both protein and mRNA levels.
Conclusions:
- Amyloid fibril formation by Abeta peptides is not a prerequisite for microglial activation.
- These findings suggest alternative mechanisms by which Abeta peptides can trigger neuroinflammatory responses in Alzheimer's disease.
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