The expanding realm of prion phenomena in neurodegenerative disease.
The aggregation of a soluble protein into insoluble, beta-sheet rich amyloid fibrils is a defining characteristic of many neurodegenerative diseases, including prion disorders. The prion protein has so far been considered unique because of its infectious nature. Recent investigations, however, suggest that other amyloid-forming proteins associated with much more common diseases, such as tau, alpha-synuclein, amyloid beta and polyglutamine proteins, while not infectious in the classical sense, share certain essential properties with prions that may explain phenotypic diversity, and patterns of spread within the nervous system. We suggest a common mechanism of pathogenesis of myriad sporadic and inherited neurodegenerative diseases based on templated conformational change.
Frost
Bess
B
Departments of Neurology and Biomedical Sciences Program, University of California, San Francisco, CA 94143-2280, USA.
Diamond
Marc I
MI
D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D006801:Humans; D008954:Models, Biological; D019636:Neurodegenerative Diseases / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D011328:Prions / Q000378:metabolism*; D011487:Protein Conformation; D051844:alpha-Synuclein / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism
D016229:Amyloid beta-Peptides; D010455:Peptides; D011328:Prions; D051844:alpha-Synuclein; D016875:tau Proteins; C097188:polyglutamine