Prion, prionoids and infectious amyloid.

"Amyloid" is a generic term and all amyloids, irrespective of amino acid sequence, are formed in a seeded nucleation mechanism in which a small aggregate (oligomers) of a few amyloid moieties (a seed or a nucleus) seed (nucleate) normal amyloid precursor moieties to change conformation to a β-sheet. All sporadic neurodegenerative disorders are diseases of old age. This epidemiological phenomenon is consistent with a view that spontaneous conformational change from soluble, monomeric precursor protein into an insoluble amyloid aggregate is accomplished via a seeded nucleation process characterized by a long lag phase. Several predictions can be made on the basis of this assumption. First, an increase of the precursor monomer concentration may favor nucleation and, thus, shorten the lag phase. Second, an increase in the number of seeds should lead to amplification of the nucleation reaction. There are several protein misfolding disorders - the most widely known include Alzheimer's disease, Parkinson's disease and other α-synucleinopathies, amyotrophic lateral sclerosis (ALS), frontotemporal dementias in which abnormally phosphorylated MAP-τ protein accumulates and finally, polyglutamine expansion diseases such as Huntington's disease and certain spinocerebellar ataxias. The proteins involved differ in each of these disorders but the molecular mechanism is almost exactly the same, a seeding-nucleation mechanism.