| Abstrakt: |
AbstractAt the interface between genes and environment, epigenetic mechanisms, including DNA methylation and histone modification, regulate neurogenic processes such as differentiation, proliferation, and maturation of neural stem cells. However, these mechanisms are altered in Alzheimer’s disease (AD), a neurodegenerative condition that mainly affects older adults. Since epigenetic mechanisms are known to be reversible, a number of molecules from natural sources are being studied as epigenetic regulators in AD. Recently, in vitroand in silicostudies have shown that C. subedentataand its alkaloids modulated neurotoxicity. However, studies exploring the epigenetic activity of these alkaloids are limited. We conducted a set of bioassays to evaluate neuronal differentiation and the sensitivity of undifferentiated SH-SY5 cells against a neurotoxic stimulus. In addition, we analyzed the methylation profiles in genes such as APP, PSI, and BACE1due to their role in amyloid processing. Docking and molecular dynamic analysis were used to explore the effect exerted by C. subedentataalkaloids on the regulation of histone deacetylases (HDAC2, HDAC3 and HDAC7). The results demonstrated that C. subedentataand galantamine induce neuronal differentiation and protect the undifferentiated SH-SY5Y cells against Aβ(1-42)-induced neurotoxicity. The methylation profiles of the studied genes show no statistically significant differences between C. subedentata,galantamine. However, these findings should be interpreted with caution, since small changes in methylation promoters in the brain could not be easily detected. Results from in silicoapproaches describe for the first time the potential promissing epigenetic effects of galantamine by regulating HDAC3 and HDAC7 modification.Communicated by Ramaswamy H. Sarma |
