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

In this study, effects of LA-GPE dimethyl ester) and GPE (Gly-L-Pro-L-Glu) on the cytotoxic action of A beta(1-42) were tested with differentiated human neuroblastoma SH-SY5Y cells as cellular Alzheimer model via measurements of mitochondria) 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 A beta(1-42) induced cell death. LA-GPE reduced A beta-induced AChE activity and oxidative stress, suggesting it as a multifunctional compound potentially valuable for the treatment of Alzheimer's disease (AD).