To be or not to be toxic: aggregations in Huntington and Alzheimer disease.
Insoluble aggregated proteins in Alzheimer disease and Huntington disease might not be pathogenic. Human studies have poor correlations between aggregates and clinical disease or pathology in these disorders, whereas mouse models have demonstrated that neuronal loss can occur in the absence of detectable aggregates. Furthermore, aggregates can exist in the absence of disease pathology in mice or symptoms in humans. Recent research suggests that soluble protein fragments, not insoluble aggregated proteins, are the toxic species in these disorders.
Slow
Elizabeth J
EJ
Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, Department of Medical Genetics, University of British Columbia, Vancouver V5Z 4H4, BC, Canada.
Graham
Rona K
RK
Hayden
Michael R
MR
D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology; D000682:Amyloid / Q000378:metabolism*; D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D006816:Huntington Disease / Q000235:genetics* / Q000473:pathology; D045586:Intranuclear Inclusion Bodies / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D016874:Neurofibrillary Tangles / Q000473:pathology*
D000682:Amyloid