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

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

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 pr...

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Bibliographic Details
Published in:International journal of molecular sciences Vol. 23; no. 15; p. 8670
Main Authors: Babylon, Lukas, Schmitt, Fabian, Franke, Yannik, Hubert, Tim, Eckert, Gunter P.
Format: Journal Article
Language:English
Published: Basel MDPI AG 04-08-2022
MDPI
Subjects:
Acids
Alzheimer disease
Alzheimer's disease
Amyloid precursor protein
Dehydrogenases
Enzymes
Folic acid
Glycolysis
L-Lactate dehydrogenase
Lactate dehydrogenase
Lactic acid
Magnesium
magnesium-orotate
Metabolism
Mitochondria
mitochondria dysfunction
Neuroprotection
Nutrients
Oxidative stress
Paralysis
Pathogenesis
Phenotypes
Physiology
Proteins
Pyridoxine
Tumor necrosis factor-TNF
Vitamin B
Vitamin B6
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Summary: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.
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content type line 23
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms23158670