Proteins constantly fold and unfold in vivo. Molecular chaperones help to ensure that a protein's final three-dimensional assembly is correct, but mistakes happen. If proteins assume unnatural conformations, they can cause any one of a family of diseases called amyloidoses, in which misfolded peptides accumulate in or around cells, forming aggregates. Most symptoms associated with systemic amyloidoses are due to the physical build-up of these amyloid deposits in vital organs.
But in neurodegenerative diseases such as Parkinson disease, spongiform encephalopathies, and Alzheimer disease (AD), the correlation isn't as direct. Experiments have implicated specific proteins in each disease – α-synuclein, prion protein, and amyloid β (Aβ), respectively – but pinning the blame on one mechanism or pathway has been difficult. In AD, researchers speculated that Aβ plaques are the culprits, making it an amyloidosis of the brain, an idea known as the amyloid hypothesis. Nevertheless, no direct link could be made ...
