β-Amyloid fibrils catalyze neurotransmitter degradation

Elad Arad, Avigail Baruch Leshem, Hanna Rapaport, Raz Jelinek

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Amyloid fibrils are one of the hallmarks of Alzheimer's disease (AD), although a causative link between plaque-forming amyloid fibrils and AD pathology remains to be clarified. This study demonstrates, for the first time for a naturally occurring amyloid, that fibrils comprising the 42-residue amyloid-β peptide (Aβ42) exhibit significant catalytic properties. Aβ42 fibrils catalyzed the hydrolysis of the model ester para-nitrophenyl acetate (pNPA) and of acetylthiocholine, a surrogate for the neurotransmitter acetylcholine. Aβ42 fibrils also catalyzed oxidation of the prominent neurotransmitters dopamine and adrenaline. Importantly, the catalytic activity was specifically manifested by mature Aβ42 fibrils and not the peptide monomers or oligomeric Aβ42, the putative neurotoxic species. Furthermore, maximal catalytic activity was recorded by the full-length Aβ42 fibrils, whereas fibrillar assemblies comprising Aβ42 subdomains were significantly less catalytic. The catalytic activity of Aβ fibrils could exhibit insidious roles in AD pathophysiology.

Original languageEnglish
Pages (from-to)908-922
Number of pages15
JournalChem Catalysis
Volume1
Issue number4
DOIs
StatePublished - 16 Sep 2021

Keywords

  • acetylcholine hydrolysis
  • Alzheimer's disease
  • dopamine oxidation
  • peptide catalysts
  • SDG3: Good health and well-being
  • β-amyloid fibrils

ASJC Scopus subject areas

  • Organic Chemistry
  • Physical and Theoretical Chemistry
  • Chemistry (miscellaneous)

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