Neurine, an acetylcholine autolysis product, elevates secreted amyloid-β protein precursor and amyloid-β peptide levels, and lowers neuronal cell viability in culture: A role in Alzheimer's disease?

David Tweedie, Arnold Brossi, De Moa Chen, Yuan Wen Ge, Jason Bailey, Qian Sheng Yu, Mohammad A. Kamal, Kumar Sambamurti, Debomoy K. Lahiri, Nigel H. Greig

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Classical hallmarks of Alzheimer's disease (AD) are a synaptic loss, cholinergic neuron death, and abnormal protein deposition, particularly of toxic amyloid-β peptide (Aβ) that is derived from amyloid-β protein precursor (AβPP) by the action of beta- and gamma-secretases. The trigger(s) initiating the biochemical cascades that underpin these hallmarks have yet to be fully elucidated. The typical forebrain cholinergic cell demise associated with AD brain results in a loss of presynaptic cholinergic markers and acetylcholine (ACh). Neurine (vinyl-trimethyl-ammonium hydroxide) is a breakdown product of ACh, consequent to autolysis and is an organic poison found in cadavre brain. The time- and concentration-dependent actions of neurine were assessed in human neuroblastoma (NB, SK-N-SH) cells in culture by quantifying cell viability by lactate dehydrogenase (LDH) and MTS assay, and AβPP and Aβ levels by Western blot and ELISA. NB cells displayed evidence of toxicity to neurine at ≥3 mg/ml, as demonstrated by elevated LDH levels in the culture media and a reduced cell viability shown by the MTS assay. Using subtoxic concentrations of neurine, elevations in AβPP and Aβ 1-40 peptide levels were detected in conditioned media samples.

Original languageEnglish (US)
Pages (from-to)9-16
Number of pages8
JournalJournal of Alzheimer's Disease
Volume10
Issue number1
DOIs
StatePublished - Jan 1 2006

Keywords

  • Acetylcholine
  • Alzheimer's disease
  • Amyloid-β peptide
  • Amyloid-β protein precursor
  • Neurine
  • Ptomaine

ASJC Scopus subject areas

  • Neuropsychology and Physiological Psychology

Fingerprint Dive into the research topics of 'Neurine, an acetylcholine autolysis product, elevates secreted amyloid-β protein precursor and amyloid-β peptide levels, and lowers neuronal cell viability in culture: A role in Alzheimer's disease?'. Together they form a unique fingerprint.

  • Cite this