(R)-α-Lipoyl-Gly-l-Pro-l-Glu dimethyl ester as dual acting agent for the treatment of Alzheimer's disease

Neuropeptides. 2017 Dec:66:52-58. doi: 10.1016/j.npep.2017.09.001. Epub 2017 Oct 2.

Abstract

In this study, effects of LA-GPE (R-α-Lipoyl-Gly-l-Pro-l-Glu dimethyl ester) and GPE (Gly-L-Pro-L-Glu) on the cytotoxic action of Aβ1-42 were tested with differentiated human neuroblastoma SH-SY5Y cells as cellular Alzheimer model via measurements of mitochondrial viability (MTT assay) and lactate dehydrogenase release (LDH assay). Effects of LA-GPE and GPE on acetylcholinesterase (AChE) activity, total antioxidant capacity (TAC) and total oxidative status (TOS) levels, and neural cell apoptosis and necrosis were also determined. In addition, biological safety of these novel formulations was evaluated in human blood cells using different cytotoxicity and genotoxicity assays. Our results indicated that both compounds could block Aβ1-42 induced cell death. LA-GPE reduced Aβ-induced AChE activity and oxidative stress, suggesting it as a multifunctional compound potentially valuable for the treatment of Alzheimer's disease (AD).

Keywords: Alzheimer's disease; Gly-pro-Glu; Lipoic acid; Tripeptides.

MeSH terms

  • Acetylcholinesterase / metabolism
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / metabolism
  • Amyloid beta-Peptides / pharmacology*
  • Apoptosis / drug effects*
  • Cell Line, Tumor
  • Humans
  • L-Lactate Dehydrogenase / metabolism
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Neuroprotective Agents / administration & dosage*
  • Neuroprotective Agents / therapeutic use
  • Oligopeptides / administration & dosage*
  • Oligopeptides / therapeutic use
  • Oxidative Stress / drug effects*
  • Peptide Fragments / pharmacology*

Substances

  • Amyloid beta-Peptides
  • Neuroprotective Agents
  • Oligopeptides
  • Peptide Fragments
  • amyloid beta-protein (1-42)
  • L-Lactate Dehydrogenase
  • Acetylcholinesterase
  • glycyl-prolyl-glutamic acid