Effects of Combining Biofactors on Bioenergetic Parameters, Aβ Levels and Survival in Alzheimer Model Organisms

Abstract

Increased amyloid beta (Aβ) levels and mitochondrial dysfunction (MD) in the human brain characterize Alzheimer disease (AD). Folic acid, magnesium and vitamin B6 are essential micro-nutrients that may provide neuroprotection. Bioenergetic parameters and amyloid precursor protein (APP) processing products were investigated in vitro in human neuroblastoma SH-SY5Y-APP695 cells, expressing neuronal APP, and in vivo, in the invertebrate Caenorhabditis elegans (CL2006 & GMC101) expressing muscular APP. Model organisms were incubated with either folic acid and magnesium-orotate (ID63) or folic acid, magnesium-orotate and vitamin B6 (ID64) in different concentrations. ID63 and ID64 reduced Aβ, soluble alpha APP (sAPPα), and lactate levels in SH-SY5Y-APP695 cells. The latter might be explained by enhanced expression of lactate dehydrogenase (LDHA). Micronutrient combinations had no effects on mitochondrial parameters in SH-SY5Y-APP695 cells. ID64 showed a significant life-prolonging effect in C. elegans CL2006. Incubation of GMC101 with ID63 significantly lowered Aβ aggregation. Both combinations significantly reduced paralysis and thus improved the phenotype in GMC101. Thus, the combinations of the tested biofactors are effective in pre-clinical models of AD by interfering with Aβ related pathways and glycolysis.

Combination of secondary plant metabolites and micronutrients against Alzheimer disease in a SH-SY5Y-APP695 cell model

“…However, our cell model is not one in which there is a deficit of Mg and Fol. Furthermore, in our studies, no increase in ATP levels was observed by the single administration of MgOr and Fol [43]. In contrast, the combination KCC increased ATP levels [source].…”

“…Reduction of Nrf-2 results in decreased MMP, decreased ATP levels and impaired mitochondrial respiration [58]. A reduction of Aβ levels by MgOr and Fol, would be also a possible explanation [43]. This could reduce the impairment of complexes by Aβ.…”

“…All substances improve the symptoms triggered by AD in different areas of AD. HstP improves mitochondrial dysfunction [42], MgOr and Fol reduce Aβ levels within cells [43] and caffeine, kahwol and cafestol (KCC) affects glycolysis [44]. In this study, we asked ourselves whether a combination of all substances leads to an improvement in all three areas of AD.…”

Therapeutic Potential of Targeting Mitochondria for Alzheimer’s Disease Treatment

“…Many studies have been carried out to identify dysfunctions affecting the quality control mechanisms of mitochondria (for refs, see [82]), giving clear evidence that all involved steps are impaired in AD pathogenesis (for refs, see [83]).…”

“…Many studies have been carried out to identify dysfunctions affecting the quality control mechanisms of mitochondria (for refs, see [82]), giving clear evidence that all involved steps are impaired in AD pathogenesis (for refs, see [83]). Although there are different localizations of toxic proteins, i.e., intra-vs. extracellular protein for Tau and Aβ, respectively, both can influence the mitochondrial function at different levels (transport, morphology and mitochondrial bioenergetics).…”