NeuroAiD® (MLC601) and Amyloid Precursor Protein Processing

Background: Amyloid precursor protein (APP) undergoes cleavage under physiological conditions, predominantly by alpha- and gamma-secretases, to form the nonpathogenic sAPP alpha and p3 fragments. By contrast, amyloid-beta (A beta) is produced via proteolytic cleavage by beta- and gamma-secretases. In Alzheimer's disease (AD), APP is preferentially processed via the amyloidogenic pathway, producing large amounts of A beta that form the major constituent of senile plaques and tau-containing neurofibrillary tangles. Similarly, stroke patients have a higher level of A beta around the area of infarct, suggesting that A beta may mediate at least some of the secondary neurotoxicity observed in stroke patients. Methods: To investigate the effects of MLC601 (NeuroAiD (R)) 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), full-length APP and secreted sAPP alpha. Results: Concentrations of MLC601 between 1 and 1,000 mu g/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 mu g/ml resulted in a significant increase in the LDH release. Treatment with 100, 500 and 1,000 mu g/ml of MLC601 significantly increases the levels of sAPP alpha secreted by SH-SY5Y into the media. Treatment with 1,000 mu g/ml of MLC601 significantly decreased the levels of full-length APP. Conclusion: MLC601 is a possible modulator of APP processing and has implications as a putative therapeutic strategy for the treatment of poststroke dementia and AD. Copyright (c) 2013 S. Karger AG, Basel