Are amyloid diseases caused by protein aggregates that mimic bacterial pore-forming toxins?
Protein fibrillization is implicated in the pathogenesis of most, if not all, age-associated neurodegenerative diseases, but the mechanism(s) by which it triggers neuronal death is unknown. Reductionist in vitro studies suggest that the amyloid protofibril may be the toxic species and that it may amplify itself by inhibiting proteasome-dependent protein degradation. Although its pathogenic target has not been identified, the properties of the protofibril suggest that neurons could be killed by unregulated membrane permeabilization, possibly by a type of protofibril referred to here as the 'amyloid pore'. The purpose of this review is to summarize the existing supportive circumstantial evidence and to stimulate further studies designed to test the validity of this hypothesis.
Lashuel
Hilal A
HA
Laboratory of Molecular Neurobiology and Neuroproteomics, Brain Mind Institute, Ecole Polytechnique Federale de Lausanne, CH-1015 Lausanne, Switzerland. hilal.lashuel@epfl.ch
Lansbury
Peter T
PT
D000375:Aging; D000544:Alzheimer Disease / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D000682:Amyloid / Q000737:chemistry / Q000502:physiology*; D016923:Cell Death; D006801:Humans; D020961:Lewy Body Disease / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D019636:Neurodegenerative Diseases / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000473:pathology*; D010300:Parkinson Disease / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D046988:Proteasome Endopeptidase Complex / Q000502:physiology
D000682:Amyloid; D046988:Proteasome Endopeptidase Complex