Related Experiment Video
Updated: Jun 11, 2026
06:49
Monitoring Protein Aggregation Kinetics In Vivo using Automated Inclusion Counting in Caenorhabditis elegans
Published on: December 17, 2021
An Aß concatemer with altered aggregation propensities.
L Giehm1, F Dal Degan, P Fraser
1Interdisciplinary Nanoscience Centre (iNANO), Center for insoluble Protein Structures (inSPIN), Department of Molecular Biology, University of Aarhus, Gustav Wieds Vej 10C, DK-8000 Aarhus C, Denmark.
Biochimica Et Biophysica Acta
|July 13, 2010
Summary
This study analyzes Con-Alz, a potential Alzheimer's disease vaccine component. Con-Alz aggregates readily but forms amorphous structures, not cytotoxic amyloid fibrils, suggesting a safer vaccine approach.
Area of Science:
- Biochemistry
- Neuroscience
- Immunology
Background:
- Alzheimer's disease (AD) is linked to amyloid-beta (Aß) peptide aggregation.
- Developing AD vaccines requires understanding Aß conformational and aggregative properties.
- Con-Alz, an Aß concatemer with T-cell epitopes, is a candidate for AD vaccine development.
Purpose of the Study:
- To investigate the conformational and aggregative properties of Con-Alz.
- To assess Con-Alz's potential for forming cytotoxic aggregates relevant to Alzheimer's disease.
- To evaluate Con-Alz's suitability for vaccine development.
Main Methods:
- Analysis of Con-Alz aggregation in the presence of denaturants and alcohols.
- Thioflavin T (ThT) binding assays to monitor aggregation.
- Electron microscopy to visualize aggregate morphology.
- Vesicle permeabilization assays to assess cytotoxicity.
Main Results:
- Con-Alz exhibits a high propensity to form aggregates, even under denaturing conditions.
- Aggregates formed by Con-Alz are amorphous and resemble truncated protofibrils, but do not form classical amyloid fibrils.
- Con-Alz does not significantly permeabilize vesicles, indicating a lack of early-stage cytotoxic oligomers.
- Sodium dodecyl sulfate (SDS) at micellar concentrations inhibited Con-Alz aggregation.
Conclusions:
- Con-Alz aggregates readily into non-classical, amorphous structures.
- The linked Aß-peptide structure may sterically hinder the formation of cytotoxic oligomers.
- Con-Alz's aggregation properties suggest a potentially safer profile for Alzheimer's disease vaccine development.
Related Concept Videos
01:57Protein Complexes with Interchangeable Parts
Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order to...
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order to...
01:57Protein Complexes with Interchangeable Parts
Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order to...
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order to...
02:41Lethal Alleles
Agouti: A Lethal Allele
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
00:41Phagocytosis
Cells pull particles inward and engulf them in spherical vesicles in an energy-requiring process called endocytosis. Phagocytosis (“cellular eating”) is one of three major types of endocytosis. Cells use phagocytosis to take in large objects—such as other cells (or their debris), bacteria, and even viruses.The objective of phagocytosis is often destruction. Cells use phagocytosis to eliminate unwelcome visitors, like pathogens (e.g., viruses and bacteria). It is perhaps unsurprising, that many...
00:41Phagocytosis
Cells pull particles inward and engulf them in spherical vesicles in an energy-requiring process called endocytosis. Phagocytosis ("cellular eating") is one of three major types of endocytosis. Cells use phagocytosis to take in large objects, such as other cells (or their debris), bacteria, and even viruses.
The objective of phagocytosis is often destruction. Cells use phagocytosis to eliminate unwelcome visitors, like pathogens (e.g., viruses and bacteria). Many immune system cells, including...
The objective of phagocytosis is often destruction. Cells use phagocytosis to eliminate unwelcome visitors, like pathogens (e.g., viruses and bacteria). Many immune system cells, including...
01:05Proteoglycans
Glycans, a class of complex heterogeneous molecules, can be covalently attached to proteins to form glycosylated proteins that regulate various physiological and pathological processes. Glycosylated proteins or glycoproteins comprise N-linked and O-linked oligosaccharides. O-glycosylation is the most common type of protein glycosylation. Here, glycans attach to the oxygen atom of the hydroxyl groups of Serine or Threonine residues. O-linked glycosylation occurs later in protein processing,...