Protein Misfolding and Degenerative Diseases

Current advances in medicine and technology are making our lives longer. Sadly, as our life expectancy increases, the chances of getting a degenerative disease like Alzheimer's, Parkinson's, or diabetes also increases. Why is this? As incredible as it might sound, these diseases are caused not by bacteria or viruses but rather by something conceptually quite simple: incorrect protein folding.

Proteins are essential for the organism because they participate in virtually every process within the cell. Therefore, if their function is impaired, the consequences can be devastating. As we age, mutations and thermodynamics (as well as some external factors) conspire against us, resulting in the misfolding of proteins.

For many proteins, the most prominent structural motif of the functional protein in its native conformation is known as the alpha helix, a right-handed spiral coil. When a protein becomes toxic, an extensive conformational change occurs and it acquires a motif known as the beta-sheet. Note that the beta sheet conformation also exists in many functional native proteins, such as the immunoglobulins, but the transition from alpha helix to beta sheet is characteristic of amyloid deposits. The abnormal conformational transition from alpha helix to beta sheet exposes hydrophobic amino acid residues and promotes protein aggregation.