The unconventional viruses of the transmissible subacute spongiform encephalopathies (kuru-CJD-GSS-FFI-scrapie-BSE) are nucleants
spontaneously generated from host precursor proteins altered to β-pleated sheet configuration that polymerize into insoluble
infectious amyloid fibrils. The
de novo conversion to infectious amyloids is facilitated or accelerated by many different point mutations causing amino acid changes,
a stop codon, or octapeptide inserts that increase the likelihood of spontaneous conversion to infectious configuration by
many orders of magnitude. Similar nucleating induction of configurational change to amyloid probably occurs in other amyloidoses
of brain and in systemic amyloidoses. Thus, all amyloids, particularly so-called fibrillar amyloid enhancing factors, may
be considered to be infectious scrapie-like agents. These events probably occur extracellularly, thus we are attempting to
reproduce them in vitro, even from synthetic polypeptides.
Index Entries Nucleation - infectious amyloids - spontaneous generation of infectious proteins - amyloidoses, of brain, nontransmissible - amyloidoses, of brain transmissible - Creutzfeldt-Jacob disease - Gerstmann-Sträussler-Scheinker disease - familial fatal insomnia - scrapie - bovine spongiform encephalopathy - amyloidoses - familial amyloidotic polyneuropathy - Alzheimer’s disease - protein configuration