Amyloidogenic properties of the prion protein fragment PrP(185-208): comparison with Alzheimer's peptide Abeta(1-28), influence of heparin and cell toxicity.
Amyloid fibrils are a hallmark of Alzheimer's and prion diseases. In both pathologies fibrils are found associated to glycosaminoglycans, modulators of the aggregation process. Amyloid peptides and proteins with very poor sequence homologies originate very similar aggregates. This implies the possible existence of a common formation mechanism. A homologous structural motif has recently been described for the Alzheimer's peptide Abeta(1-28) and the prion protein fragment PrP(185-208). We have studied the influence histidine residues and heparin on the aggregation process of both peptides and determined the possible amyloid characteristics of PrP(185-208), still unknown. The results show that PrP(185-208) forms amyloid aggregates in the presence of heparin. Histidines influence the aggregation kinetics, as in Abeta(1-28), although to a lesser extent. Other spectroscopic properties of the PrP(185-208) fragment are shown to be equivalent to those of other amyloid peptides and PrP(185-208) is shown to be cytotoxic using a neuroblastoma cell line.
Cortijo-Arellano
Marta
M
Biophysics Unit and Centre of Studies in Biophysics, Department of Biochemistry and Molecular Biology, Autonomous University of Barcelona, 08193 Bellaterra, Spain.
Ponce
Jovita
J
Durany
Núria
N
Cladera
Josep
J
D000682:Amyloid / Q000737:chemistry*; D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000737:chemistry*; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006493:Heparin / Q000494:pharmacology; D006639:Histidine / Q000737:chemistry; D006801:Humans; D009447:Neuroblastoma / Q000473:pathology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000737:chemistry*; D018621:PrPC Proteins / Q000008:administration & dosage / Q000737:chemistry*
D000682:Amyloid; D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D018621:PrPC Proteins; C084358:amyloid beta-protein (1-28); C524422:prion protein (185-208); D006639:Histidine; D006493:Heparin