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?
Titel:
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?
Auteur:
Tweedie, David Brossi, Arnold Chen, DeMoa Ge, Yuan-Wen Bailey, Jason Yu, Qian-sheng Kamal, Mohammad A. Sambamurti, Kumar Lahiri, Debomoy K. Greig, Nigel H.
Verschenen in:
Journal of Alzheimer's disease
Paginering:
Jaargang 10 (2006) nr. 1 pagina's 9-16
Jaar:
2006-09-14
Inhoud:
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.