Related Experiment Video
Updated: Jul 18, 2026
10:08
Purification and Aggregation of the Amyloid Precursor Protein Intracellular Domain
Published on: August 28, 2012
Structure, function and amyloidogenic propensity of apolipoprotein A-I
Laura Obici1, Guido Franceschini, Laura Calabresi
1Centro per lo Studio e la Cura delle Amiloidosi Sistemiche, Laboratorio di Biotecnologie, IRCCS Policlinico San Matteo, Pavia, Italy.
Summary
Apolipoprotein A-I (ApoA-I) normally prevents cholesterol buildup but can cause amyloidosis due to mutations. Understanding ApoA-I structure and function is key to preventing this disease.
Area of Science:
- Biochemistry
- Molecular Biology
- Cardiovascular Science
Background:
- Apolipoprotein A-I (ApoA-I) is crucial for high-density lipoproteins (HDL) and cholesterol homeostasis.
- Mutations in ApoA-I can lead to systemic amyloidosis and localization of fibrils in atherosclerotic plaques.
- The complex structure, folding, and metabolism of ApoA-I are not fully understood, hindering clarification of its amyloid transition.
Purpose of the Study:
- To review current knowledge on ApoA-I structure, function, and amyloidogenic potential.
- To highlight molecular mechanisms contributing to ApoA-I-related amyloidosis pathogenesis.
- To identify insights from comparative studies of wild-type, amyloidogenic, and non-amyloidogenic variants.
Main Methods:
- Literature review of existing research on Apolipoprotein A-I.
- Comparative analysis of wild-type versus amyloidogenic ApoA-I properties.
- Examination of ApoA-I variants associated with hypoalphalipoproteinemia without amyloidosis.
Main Results:
- ApoA-I's protective role against cholesterol accumulation is well-established.
- Specific amino acid substitutions in ApoA-I can induce systemic amyloidosis.
- The wild-type ApoA-I molecule exhibits an intrinsic tendency to form amyloid fibrils within atherosclerotic plaques.
Conclusions:
- Understanding ApoA-I's complex structure, folding, and metabolism is essential for elucidating its amyloid transition.
- Comparative studies of ApoA-I variants provide crucial insights into amyloidogenesis mechanisms.
- Further research into ApoA-I's structure-function relationship is vital for understanding and potentially treating amyloid-related diseases.
Related Concept Videos
03:03Amyloid Fibrils
Amyloid fibrils are aggregates of misfolded proteins. Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils.
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
03:03Amyloid Fibrils
Amyloid fibrils are aggregates of misfolded proteins. Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils.
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
01:25Protein Folding
Proteins are chains of amino acids linked together by peptide bonds. Upon synthesis, a protein folds into a three-dimensional conformation, critical to its biological function. Interactions between its constituent amino acids guide protein folding, and hence the protein structure is primarily dependent on its amino acid sequence.
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...
01:22Protein Folding
Overview
01:23Alzheimer Disease ll: Pathophysiology
Alzheimer disease involves structural changes in the brain that begin long before symptoms appear. The most distinctive features are extracellular neuritic plaques and intracellular neurofibrillary tangles.Neuritic plaques form in the cerebral cortex and around blood vessels. These plaques contain a dense core of beta-amyloid (Aβ)—a toxic protein fragment that clumps outside neurons. The core is surrounded by damaged neuronal extensions, as well as reactive astrocytes and microglia. Abnormal...
02:15Protein and Protein Structure
Proteins are one of the most abundant organic molecules in living systems and have the most diverse range of functions of all macromolecules. Proteins may be structural, regulatory, contractile, or protective. They may serve in transport, storage, or membranes; or they may be toxins or enzymes. Their structures, like their functions, vary greatly. They are all, however, amino acid polymers arranged in a linear sequence.
A protein's shape is critical to its function. For example, an enzyme can...
A protein's shape is critical to its function. For example, an enzyme can...