Effect of DHA and coenzymeQ10 against Aβ- and zinc-induced mitochondrial dysfunction in human neuronal cells.
BACKGROUND
Beta-amyloid (Aβ) protein is a key factor in the pathogenesis of Alzheimer's disease (AD) and it has been reported that mitochondria is involved in the biochemical pathway by which Aβ can lead to neuronal dysfunction. Coenzyme Q10 (CoQ10) is an essential cofactor involved in the mitochondrial electron transport chain and has been suggested as a potential therapeutic agent in AD. Zinc toxicity also affects cellular energy production by decreasing oxygen consumption rate (OCR) and ATP turnover in human neuronal cells, which can be restored by the neuroprotective effect of docosahexaenoic acid (DHA).


METHODS
In the present study, using Seahorse XF-24 Metabolic Flux Analysis we investigated the effect of DHA and CoQ10 alone and in combination against Aβ- and zinc-mediated changes in the mitochondrial function of M17 neuroblastoma cell line.


RESULTS
Here, we observed that DHA is specifically neuroprotective against zinc-triggered mitochondrial dysfunction, but does not directly affect Aβ neurotoxicity. CoQ10 has shown to be protective against both Aβ- and zinc-induced alterations in mitochondrial function.


CONCLUSIONS
Our results indicate that DHA and CoQ10 may be useful for the prevention, treatment and management of neurodegenerative diseases such as AD.
NeuroAllergy Research Laboratory (NARL), School of Medicine, Deakin University, Waurn Ponds, Australia.
Nadia
N
Sadli
Colin J
CJ
Barrow
Sean
S
McGee
Cenk
C
Suphioglu
D016229:Amyloid beta-Peptides / Q000633:toxicity*; D002460:Cell Line; D045744:Cell Line, Tumor; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D004338:Drug Combinations; D006801:Humans; D008928:Mitochondria / Q000737:chemistry / Q000187:drug effects*; D009474:Neurons / Q000737:chemistry / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology; D015032:Zinc / Q000633:toxicity*
D016229:Amyloid beta-Peptides; D004338:Drug Combinations; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D014451:Ubiquinone; D004281:Docosahexaenoic Acids; C024989:coenzyme Q10; D015032:Zinc