Spontaneous generation of infectious nucleating amyloids in the transmissible and nontransmissible cerebral amyloidoses.
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 beta-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.
Gajdusek
D C
DC
Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism; D000682:Amyloid / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017772:Amyloid Neuropathies / Q000235:genetics / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000686:Amyloidosis / Q000235:genetics / Q000378:metabolism*; D004252:DNA Mutational Analysis; D005006:Ethnicity / Q000235:genetics; D005796:Genes; D020022:Genetic Predisposition to Disease; D014943:Global Health; D006801:Humans; D015994:Incidence; D017354:Point Mutation; D011108:Polymers; D011228:Prealbumin / Q000235:genetics / Q000378:metabolism; D017096:Prion Diseases / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics / Q000378:metabolism* / Q000635:transmission; D017510:Protein Folding; D011499:Protein Processing, Post-Translational; D017433:Protein Structure, Secondary
D000682:Amyloid; D016564:Amyloid beta-Protein Precursor; D011108:Polymers; D011228:Prealbumin