NR ARBU
AU Bucciantini,M.; Giannoni,E.; Chiti,F.; Baroni,F.; Formigli,L.; Zurdo,J.; Taddei,N.; Ramponi,G.; Dobson,C.M.; Stefani,M.
TI Inherent toxicity of aggregates implies a common mechanism for protein misfolding diseases
QU Nature 2002 Apr 4; 416(6880): 507-11
KI Nature. 2002 Apr 4;416(6880):483-4. PMID: 11932723
PT journal article
AB A range of human degenerative conditions, including Alzheimer's disease, light-chain amyloidosis and the spongiform encephalopathies, is associated with the deposition in tissue of proteinaceous aggregates known as amyloid fibrils or plaques. It has been shown previously that fibrillar aggregates that are closely similar to those associated with clinical amyloidoses can be formed in vitro from proteins not connected with these diseases, including the SH3 domain from bovine phosphatidyl-inositol-3'-kinase and the amino-terminal domain of the Escherichia coli HypF protein. Here we show that species formed early in the aggregation of these non-disease-associated proteins can be inherently highly cytotoxic. This finding provides added evidence that avoidance of protein aggregation is crucial for the preservation of biological function and suggests common features in the origins of this family of protein deposition diseases.
MH 1-Phosphatidylinositol 3-Kinase/chemistry/metabolism/ultrastructure; 3T3 Cells; Alzheimer Disease/etiology/pathology; Animals; Bacterial Proteins/chemistry/toxicity/ultrastructure; Cytotoxins; Evolution; Human; Mice; Neurodegenerative Diseases/*etiology/metabolism; PC12 Cells; *Protein Folding; Rats; Recombinant Proteins/chemistry; Senile Plaques/*chemistry/metabolism; Support, Non-U.S. Gov't; src Homology Domains
AD Dipartimento di Scienze Biochimiche, Viale Morgagni 50, Universita degli Studi di Firenze, 50134 Firenze, Italy.
SP englisch
PO England