title: NeuroAiD® (MLC601) and amyloid precursor protein processing.
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.
  
  
  CONCLUSIONS
  MLC601 is a possible modulator of APP processing and has implications as a putative therapeutic strategy for the treatment of poststroke dementia and AD.
authors.affiliation: Memory, Aging and Cognition Centre, National University Health System, National University of Singapore, Singapore.
authors.forename: Y A
authors.initials: YA
authors.lastname: Lim
authors.forename: L A
authors.initials: LA
authors.lastname: Murray
authors.forename: M K P
authors.initials: MK
authors.lastname: Lai
authors.forename: C
authors.initials: C
authors.lastname: Chen
mesh_terms: D000199:Actins / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D003470:Culture Media / Q000032:analysis; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*
chemical_list: D000199:Actins; D016564:Amyloid beta-Protein Precursor; D003470:Culture Media; D004365:Drugs, Chinese Herbal; C546417:Neuroaid; D018696:Neuroprotective Agents; D007770:L-Lactate Dehydrogenase