NeuroAiD (R) (MLC601) and Amyloid Precursor Protein Processing
Lim, YA Murray, LA Lai, MKP Chen, C
Lim, YA
Murray, LA
Chen, C
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Abstract
Background: Amyloid precursor protein (APP) undergoes cleavage under physiological conditions, predominantly by α- and γ-secretases, to form the nonpathogenic sAPPα and p3 fragments. By contrast, amyloid-beta (Aβ) is produced via proteolytic cleavage by β- and 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), full-length 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 release. Treatment with 100, 500 and 1,000 μg/ml of MLC601 significantly increases the levels of sAPPα secreted by SH-SY5Y into the media. Treatment with 1,000 μg/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 © 2013 S. Karger AG, Basel.
Keywords
Science & Technology, Life Sciences & Biomedicine, Clinical Neurology, Peripheral Vascular Disease, Neurosciences & Neurology, Cardiovascular System & Cardiology, Alzheimer's disease, Stroke, Amyloid precursor protein, MLC601, NeuroAiD, SALVIANOLIC-ACID-B, ALPHA-SECRETASE, BETA-SECRETASE, OXIDATIVE STRESS, CHINESE MEDICINE, FERULIC ACID, ACTIVATION, TAU, TOXICITY, NEUROTOXICITY
Source Title
CEREBROVASCULAR DISEASES
Publisher
KARGER
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Date
2013-01-01
DOI
10.1159/000346236
Type
Article