Protein aggregation

Protein aggregation is a biological phenomenon where misfolded proteins aggregate (i.e., accumulate and clump together) in the form of insoluble fibrils leading to cell damage and the development of protein aggregation diseases.

Overview

In biological systems, proteins are large biomolecules, or macromolecules, consisting of one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, responding to stimuli, providing structure to cells and organisms, and transporting molecules from one location to another.

Protein aggregation is usually associated with conformational disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease, Amyotrophic lateral sclerosis, and prion diseases. In these diseases, certain proteins become misfolded, which makes them prone to aggregate.

Causes

Protein aggregation is primarily caused by the overproduction of a certain protein or its exposure to various external factors that can disrupt its structure. These factors include changes in pH, temperature, ionic strength, or the presence of certain chemicals. When a protein is denatured due to such factors, it exposes its hydrophobic core, which is usually buried in the interior of the protein to avoid contact with the hydrophilic environment.

Consequences

The aggregation of misfolded proteins can disrupt cell function and lead to cell death. This is because protein aggregates can interfere with various cellular processes. They can disrupt the function of cellular organelles, interfere with cell signaling, cause oxidative stress, and trigger inflammatory responses.

Treatment

The treatment of protein aggregation diseases is currently focused on preventing the formation of protein aggregates. This can be achieved by enhancing the protein folding machinery of the cell or by promoting the degradation of misfolded proteins.

See also

• Protein folding
• Protein homeostasis
• Chaperone (protein)

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