Neurine, an acetylcholine autolysis product, elevates secreted amyloid-beta protein precursor and amyloid-beta peptide levels, and lowers neuronal cell viability in culture: a role in Alzheimer's disease?
Classical hallmarks of Alzheimer's disease (AD) are a synaptic loss, cholinergic neuron death, and abnormal protein deposition, particularly of toxic amyloid-beta peptide (Abeta) that is derived from amyloid-beta protein precursor (AbetaPP) 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 AbetaPP and Abeta levels by Western blot and ELISA. NB cells displayed evidence of toxicity to neurine at > or = 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 AbetaPP and Abeta1-40 peptide levels were detected in conditioned media samples.
Tweedie
David
D
Section on Drug Design and Delivery, Laboratory of Neurosciences, Intramural Research Program, National Institute on Aging, Baltimore, MD 21224, USA.
Brossi
Arnold
A
Chen
DeMoa
D
Ge
Yuan-Wen
YW
Bailey
Jason
J
Yu
Qian-Sheng
QS
Kamal
Mohammad A
MA
Sambamurti
Kumar
K
Lahiri
Debomoy K
DK
Greig
Nigel H
NH
D000109:Acetylcholine / Q000378:metabolism*; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000096:biosynthesis*; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis*; D001329:Autolysis / Q000503:physiopathology*; D015153:Blotting, Western; D019062:Cell Adhesion Molecules, Neuron-Glia / Q000032:analysis / Q000378:metabolism / Q000502:physiology*; D018929:Cell Culture Techniques; D016923:Cell Death / Q000502:physiology; D049109:Cell Proliferation; D002470:Cell Survival / Q000502:physiology; D006801:Humans; D007770:L-Lactate Dehydrogenase; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000473:pathology*; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000473:pathology
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D019062:Cell Adhesion Molecules, Neuron-Glia; C103810:neurin-1; D007770:L-Lactate Dehydrogenase; D000109:Acetylcholine