Babylon 2022 Int J Mol Sci

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Babylon L, Schmitt F, Franke Y, Hubert T, Eckert GP (2022) Effects of combining biofactors on bioenergetic parameters, AΞ² levels and survival in Alzheimer model organisms. https://doi.org/10.3390/ijms23158670

Β» Int J Mol Sci 23:8670. PMID: 35955803 Open Access

Babylon Lukas, Schmitt Fabian, Franke Yannik, Hubert Tim, Eckert Gunter P (2022) Int J Mol Sci

Abstract: Increased amyloid beta (AΞ²) 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 AΞ², soluble alpha APP (sAPPΞ±), 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 AΞ² 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 AΞ² related pathways and glycolysis. β€’ Keywords: Alzheimer disease, C. elegans, Amyloid beta, Biofactor, Folic acid, Magnesium-orotate, Mitochondria, Mitochondria dysfunction, Vitamin B6 β€’ Bioblast editor: Plangger M β€’ O2k-Network Lab: DE Giessen Eckert GP


Labels: MiParea: Respiration  Pathology: Alzheimer's 

Organism: Human  Tissue;cell: Neuroblastoma  Preparation: Permeabilized cells 


Coupling state: LEAK, OXPHOS, ET  Pathway: N, S, CIV, NS, ROX  HRR: Oxygraph-2k 

2022-11 

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