Related Experiment Video
Updated: Jul 1, 2025
Rapid Generation of Amyloid from Native Proteins In vitro
Published on: December 5, 2013
Structure of cytotoxic amyloid oligomers generated during disaggregation
Toshisuke Kaku1, Kazunori Ikebukuro1, Kaori Tsukakoshi1
1Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, 2-24-16 Naka-cho, Koganei, Tokyo 184-8588, Japan.
Abstract:
Amyloidosis is characterized by the abnormal accumulation of amyloid proteins. The causative proteins aggregate from monomers to oligomers and fibrils, among which some intermediate oligomers are considered as major toxins. Cytotoxic oligomers are generated not only by aggregation but also via fibril disaggregation. However, little is known about the structural characteristics and generation conditions of cytotoxic oligomers produced during disaggregation. Herein, we summarized the structural commonalities of cytotoxic oligomers formed under various disaggregation conditions, including the addition of heat shock proteins or small compounds. In vitro experimental data demonstrated the presence of high-molecular-weight oligomers (protofibrils or protofilaments) that exhibited a fibrous morphology and β-sheet structure. Molecular dynamics simulations indicated that the distorted β-sheet structure contributed to their metastability. The tendency of these cytotoxic oligomers to appear under mild disaggregation conditions, implied formation during the early stages of disaggregation. This review will aid researchers in exploring the characteristics of highly cytotoxic oligomers and developing drugs that target amyloid aggregates.
Insights
Cytotoxic amyloid oligomers, implicated in disease, can form during fibril disaggregation. These toxic species exhibit fibrous structures and metastability, offering new therapeutic targets.
Area of Science:
- Biochemistry
- Molecular Biology
- Structural Biology
Background:
- Amyloidosis involves abnormal amyloid protein accumulation.
- Intermediate amyloid oligomers are key toxins.
- Oligomers form via aggregation and fibril disaggregation.
Purpose of the Study:
- To summarize structural commonalities of cytotoxic oligomers formed during disaggregation.
- To investigate the generation conditions of these toxic oligomers.
- To provide insights for developing drugs targeting amyloid aggregates.
Main Methods:
- Literature review of cytotoxic oligomer formation.
- In vitro experiments with heat shock proteins and small compounds.
- Molecular dynamics simulations of oligomer structures.
Main Results:
- High-molecular-weight oligomers (protofibrils/protofilaments) with fibrous morphology and β-sheet structure were identified.
- Distorted β-sheet structures contribute to oligomer metastability.
- Cytotoxic oligomers form during early stages of disaggregation under mild conditions.
Conclusions:
- Understanding cytotoxic oligomer characteristics is crucial for amyloidosis research.
- Targeting these specific oligomers may lead to novel therapeutic strategies.
- This review aids in exploring and developing drugs against toxic amyloid aggregates.
More Related Videos
08:53Characterization of pH-Dependent Reversible Self-Assembly of Amyloid Beta 1-40-Coated Gold Colloids
Published on: March 21, 2025
10:10Use of Two Dimensional Semi-denaturing Detergent Agarose Gel Electrophoresis to Confirm Size Heterogeneity of Amyloid or Amyloid-like Fibers
Published on: April 26, 2018
Related Concept Videos
03:03Amyloid Fibrils
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
01:22Protein Folding