Acetylcholinesterase triggers the aggregation of PrP 106-126

Journal Article · Fri Jul 21 00:00:00 EDT 2006 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/j.bbrc.2006.04.187· OSTI ID:20854365

Pera, M ^[1]; Roman, S ^[1]; Ratia, M ^[1]; Camps, P ^[2]; Munoz-Torrero, D ^[2]; Colombo, L ^[3]; Manzoni, C ^[3]; Salmona, M ^[3]; Badia, A ^[1]; Clos, M V ^[1]

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1. Departament de Farmacologia, de Terapeutica i de Toxicologia, Institut Neurociencies, Universitat Autonoma de Barcelona, Barcelona (Spain)
2. Laboratori de Quimica Farmaceutica (Unitat Associada al CSIC), Facultat de Farmacia, Universitat de Barcelona, Barcelona (Spain)
3. Department of Molecular Biochemistry and Pharmacology, Istituto di Ricerche Farmacologiche 'Mario Negri', Milan (Italy)

Acetylcholinesterase (AChE), a senile plaque component, promotes amyloid-{beta}-protein (A{beta}) 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 A{beta} 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.

• OSTI ID: 20854365
• Journal Information: Biochemical and Biophysical Research Communications, Vol. 346, Issue 1; Other Information: DOI: 10.1016/j.bbrc.2006.04.187; PII: S0006-291X(06)01131-4; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
AGGLOMERATION
COUMARIN
FLUORESCENCE
IN VITRO
INHIBITION
IODIDES
MICROSCOPY
NERVOUS SYSTEM DISEASES
PEPTIDES