Acetylcholinesterase triggers the aggregation of PrP 106-126.
Acetylcholinesterase (AChE), a senile plaque component, promotes amyloid-beta-protein (Abeta) fibril formation in vitro. The presence of prion protein (PrP) in Alzheimer's disease (AD) senile plaques prompted us to assess if AChE could trigger the PrP peptides aggregation as well. Consequently, the efficacy of AChE on the PrP peptide spanning-residues 106-126 aggregation containing a coumarin fluorescence probe (coumarin-PrP 106-126) was studied. Kinetics of coumarin-PrP 106-126 aggregation showed a significant increase of maximum size of aggregates (MSA), which was dependent on AChE concentration. AChE-PrP 106-126 aggregates showed the tinctorial and optical amyloid properties as determined by polarized light and electronic microscopy analysis. A remarkable inhibition of MSA was obtained with propidium iodide, suggesting that AChE triggers PrP 106-126 and Abeta aggregation through a similar mechanism. Huprines (AChE inhibitors) also significantly decreased MSA induced by AChE as well, unveiling the potential interest for some AChE inhibitors as a novel class of potential anti-prion drugs.
Pera
M
M
Departament de Farmacologia, de Terapèutica i de Toxicología, Institut Neurociències, Universitat Autónoma de Barcelona, Barcelona, Spain.
Román
S
S
Ratia
M
M
Camps
P
P
Muñoz-Torrero
D
D
Colombo
L
L
Manzoni
C
C
Salmona
M
M
Badia
A
A
Clos
M V
MV
D000110:Acetylcholinesterase / Q000378:metabolism*; D000470:Alkaloids; D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D003374:Coumarins; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology; D006801:Humans; D008856:Microscopy, Fluorescence; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D011328:Prions / Q000737:chemistry* / Q000378:metabolism; D011419:Propidium / Q000494:pharmacology; D017433:Protein Structure, Secondary / Q000187:drug effects; D012717:Sesquiterpenes / Q000494:pharmacology
D000470:Alkaloids; D000634:Aminoquinolines; D002800:Cholinesterase Inhibitors; D003374:Coumarins; D006576:Heterocyclic Compounds, 4 or More Rings; D010446:Peptide Fragments; D011328:Prions; D012717:Sesquiterpenes; C404518:huprine X; C404519:huprine Y; C082632:prion protein (106-126); C050426:huperzine A; D011419:Propidium; D000110:Acetylcholinesterase