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?

Article type: Research Article

Authors: Tweedie, David^a | Brossi, Arnold^b | Chen, DeMoa^c | Ge, Yuan-Wen^c | Bailey, Jason^c | Yu, Qian-sheng^a | Kamal, Mohammad A.^d | Sambamurti, Kumar^{e; **} | Lahiri, Debomoy K.^{c; **} | Greig, Nigel H.^{a; *; **}

Affiliations: [a] Section on Drug Design and Delivery, Laboratory of Neurosciences, Intramural Research Program, National Institute on Aging, Baltimore, MD 21224, USA | [b] School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA | [c] Department of Psychiatry, Institute Psychiatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA | [d] Enzymoics, 7 Peterlee P1., Habersham, NSW 2770, Australia | [e] Department of Physiology and Neuroscience, Medical University of South Carolina, Charleston, SC 29464, USA

Correspondence: [*] Corresponding author: Nigel H. Greig, Drug Design & Development Section, Gerontology Research Center, 5600 Nathan Shock Dr., Baltimore, MD 21224, USA. E-mail: Greign@grc.nia.nih.gov.

Note: [**] Equal contribution between these authors.

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 Aβ1-40 peptide levels were detected in conditioned media samples.

Keywords: Alzheimer's disease, neurine, amyloid-β protein precursor, amyloid-β peptide, acetylcholine, ptomaine

DOI: 10.3233/JAD-2006-10102

Journal: Journal of Alzheimer's Disease, vol. 10, no. 1, pp. 9-16, 2006