Acetylcholinesterase as an amyloid enhancing factor in PrP82-146 aggregation process

M. Pera, A. Martínez-Otero, L. Colombo, M. Salmona, D. Ruiz-Molina, A. Badia, M. V. Clos

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Acetylcholinesterase (AChE) triggers beta amyloid plaques formation and is associated with amyloid plaques in the brain. Recent studies have demonstrated that AChE promotes the aggregation of PrP106-126, a peptide deduced from the prion protein sequence. In the present study we show that AChE triggers also the fibrillization of the main component of the amyloid plaques -the peptide spanning residues 82-146 (PrP82-146)- found in patients with Gerstmann-Sträussler-Scheinker disease (GSS). The kinetics of PrP82-146 aggregate formation was directly correlated with AChE concentration and mature fibrils showed the tinctorial and optical properties of amyloid. Atomic force microscopy analysis showed that oligomer and amyloid fibril formation were significantly accelerated by AChE. This effect was mediated by the peripheral site of the enzyme since propidium iodide inhibited the fibrillization process. Present results strongly support the role of AChE in triggering amyloidogenesis and the potential therapeutic relevance of peripheral site blocker compounds.

Original languageEnglish
Pages (from-to)217-224
Number of pages8
JournalMolecular and Cellular Neuroscience
Volume40
Issue number2
DOIs
Publication statusPublished - Feb 2009

Fingerprint

Acetylcholinesterase
Amyloid Plaques
Amyloid
Peptides
Propidium
Atomic Force Microscopy
amyloid enhancing factor
Staining and Labeling
Brain
Enzymes

Keywords

  • Acetylcholinesterase
  • AChE peripheral site
  • AChE peripheral site blockers
  • Amyloid aggregation process
  • Gerstmann-Sträussler-Scheinker disease
  • Prion protein
  • PrP82-146

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Cell Biology

Cite this

Acetylcholinesterase as an amyloid enhancing factor in PrP82-146 aggregation process. / Pera, M.; Martínez-Otero, A.; Colombo, L.; Salmona, M.; Ruiz-Molina, D.; Badia, A.; Clos, M. V.

In: Molecular and Cellular Neuroscience, Vol. 40, No. 2, 02.2009, p. 217-224.

Research output: Contribution to journalArticle

Pera, M. ; Martínez-Otero, A. ; Colombo, L. ; Salmona, M. ; Ruiz-Molina, D. ; Badia, A. ; Clos, M. V. / Acetylcholinesterase as an amyloid enhancing factor in PrP82-146 aggregation process. In: Molecular and Cellular Neuroscience. 2009 ; Vol. 40, No. 2. pp. 217-224.
@article{cd7a2e8c9f124efba04354dcd331f697,
title = "Acetylcholinesterase as an amyloid enhancing factor in PrP82-146 aggregation process",
abstract = "Acetylcholinesterase (AChE) triggers beta amyloid plaques formation and is associated with amyloid plaques in the brain. Recent studies have demonstrated that AChE promotes the aggregation of PrP106-126, a peptide deduced from the prion protein sequence. In the present study we show that AChE triggers also the fibrillization of the main component of the amyloid plaques -the peptide spanning residues 82-146 (PrP82-146)- found in patients with Gerstmann-Str{\"a}ussler-Scheinker disease (GSS). The kinetics of PrP82-146 aggregate formation was directly correlated with AChE concentration and mature fibrils showed the tinctorial and optical properties of amyloid. Atomic force microscopy analysis showed that oligomer and amyloid fibril formation were significantly accelerated by AChE. This effect was mediated by the peripheral site of the enzyme since propidium iodide inhibited the fibrillization process. Present results strongly support the role of AChE in triggering amyloidogenesis and the potential therapeutic relevance of peripheral site blocker compounds.",
keywords = "Acetylcholinesterase, AChE peripheral site, AChE peripheral site blockers, Amyloid aggregation process, Gerstmann-Str{\"a}ussler-Scheinker disease, Prion protein, PrP82-146",
author = "M. Pera and A. Mart{\'i}nez-Otero and L. Colombo and M. Salmona and D. Ruiz-Molina and A. Badia and Clos, {M. V.}",
year = "2009",
month = "2",
doi = "10.1016/j.mcn.2008.10.008",
language = "English",
volume = "40",
pages = "217--224",
journal = "Molecular and Cellular Neurosciences",
issn = "1044-7431",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - Acetylcholinesterase as an amyloid enhancing factor in PrP82-146 aggregation process

AU - Pera, M.

AU - Martínez-Otero, A.

AU - Colombo, L.

AU - Salmona, M.

AU - Ruiz-Molina, D.

AU - Badia, A.

AU - Clos, M. V.

PY - 2009/2

Y1 - 2009/2

N2 - Acetylcholinesterase (AChE) triggers beta amyloid plaques formation and is associated with amyloid plaques in the brain. Recent studies have demonstrated that AChE promotes the aggregation of PrP106-126, a peptide deduced from the prion protein sequence. In the present study we show that AChE triggers also the fibrillization of the main component of the amyloid plaques -the peptide spanning residues 82-146 (PrP82-146)- found in patients with Gerstmann-Sträussler-Scheinker disease (GSS). The kinetics of PrP82-146 aggregate formation was directly correlated with AChE concentration and mature fibrils showed the tinctorial and optical properties of amyloid. Atomic force microscopy analysis showed that oligomer and amyloid fibril formation were significantly accelerated by AChE. This effect was mediated by the peripheral site of the enzyme since propidium iodide inhibited the fibrillization process. Present results strongly support the role of AChE in triggering amyloidogenesis and the potential therapeutic relevance of peripheral site blocker compounds.

AB - Acetylcholinesterase (AChE) triggers beta amyloid plaques formation and is associated with amyloid plaques in the brain. Recent studies have demonstrated that AChE promotes the aggregation of PrP106-126, a peptide deduced from the prion protein sequence. In the present study we show that AChE triggers also the fibrillization of the main component of the amyloid plaques -the peptide spanning residues 82-146 (PrP82-146)- found in patients with Gerstmann-Sträussler-Scheinker disease (GSS). The kinetics of PrP82-146 aggregate formation was directly correlated with AChE concentration and mature fibrils showed the tinctorial and optical properties of amyloid. Atomic force microscopy analysis showed that oligomer and amyloid fibril formation were significantly accelerated by AChE. This effect was mediated by the peripheral site of the enzyme since propidium iodide inhibited the fibrillization process. Present results strongly support the role of AChE in triggering amyloidogenesis and the potential therapeutic relevance of peripheral site blocker compounds.

KW - Acetylcholinesterase

KW - AChE peripheral site

KW - AChE peripheral site blockers

KW - Amyloid aggregation process

KW - Gerstmann-Sträussler-Scheinker disease

KW - Prion protein

KW - PrP82-146

UR - http://www.scopus.com/inward/record.url?scp=59049092791&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=59049092791&partnerID=8YFLogxK

U2 - 10.1016/j.mcn.2008.10.008

DO - 10.1016/j.mcn.2008.10.008

M3 - Article

VL - 40

SP - 217

EP - 224

JO - Molecular and Cellular Neurosciences

JF - Molecular and Cellular Neurosciences

SN - 1044-7431

IS - 2

ER -