(MLC601) and Amyloid Precursor Protein Processing

Background: Amyloid precursor protein (APP) undergoes cleavage under physiological conditions, predominantly by αand γ-secretases, to form the nonpathogenic sAPPα and p3 fragments. By contrast, amyloid-beta (Aβ) is produced via proteolytic cleavage by βand γ-secretases. In Alzheimer’s disease (AD), APP is preferentially processed via the amyloidogenic pathway, producing large amounts of Aβ that form the major constituent of senile plaques and tau-containing neurofibrillary tangles. Similarly, stroke patients have a higher level of Aβ around the area of infarct, suggesting that Aβ may mediate at least some of the secondary neurotoxicity observed in stroke patients. Methods: To investigate the effects of MLC601 (NeuroAiD ® ) on regulation of APP processing, the human neuroblastoma cell line SH-SY5Y was used for all experiments. Stocks of MLC601 were prepared at a final concentration of 50 mg/ml. Cells were treated with different concentrations of MLC601 before assessing changes in the levels of released lactate dehydrogenase (LDH), fulllength APP and secreted sAPPα. Results: Concentrations of MLC601 between 1 and 1,000 μg/ml significantly lowered the levels of LDH released into the media when compared to control cells. In contrast, MLC601 concentrations at 5,000 and 10,000 μg/ml resulted in a significant increase in the LDH Published online: March 14, 2013 Christopher Chen Department of Pharmacology, Yong Loo Lin School of Medicine National University of Singapore Singapore (Singapore) E-Mail phccclh @ nus.edu.sg © 2013 S. Karger AG, Basel 1015–9770/13/0357–0030$38.00/0