Effect of DHA and CoenzymeQ10 Against A�- and Zinc-Induced Mitochondrial Dysfunction in Human Neuronal Cells

Abstract

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). Method: 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. Conclusion: Our results indicate that DHA and CoQ10 may be useful for the prevention, treatment and management of neurodegenerative diseases such as AD.

Significance of cytosolic cathepsin D in Alzheimer's disease pathology: Protective cellular effects of PLGA nanoparticles against β‐amyloid‐toxicity

“…Our lysotracker labelling further revealed that pepstatin A partly attenuated diffuse labelling of neurons observed after Ab treatment ( Figure 5I-K). In parallel, we showed that Ab 1-42 toxicity, as reported in earlier studies [76,77], was significantly attenuated following treatment with antioxidant CoQ10. Concurrently the levels of carbonylated proteins and CatD were reduced ( Figure S4).…”

Omega-3 fatty acid obtained from Nannochloropsis oceanica cultures grown under low urea protect against Abeta-induced neural damage

“…These findings indicate that Abeta induced cell death in neuro-2A cells. Recently, unsaturated fatty acids including DHA and EPA have been shown to protect against AD and neuronal cell damage (Sadli et al 2013;Swanson et al 2012). Our results indicate that the cell viability of Abita-treated neuro-2A cells could be improved by treatment with extracts of Nannochloropsis oceanica from Group II (Fig.…”

“…These omega-3 unsaturated fatty acids have been reported to protect against Alzheimer's disease (AD) (Sadli et al 2013;Sahlin et al 2007), and against oxidative stress in neural cells (Yang et al 2012). Recently, omega-6 unsaturated fatty acids such as arachidonic acid and linoleic acid have been found to play a role in the development of inflammation (Al-Taan et al 2013).…”

“Iron free” zinc oxide nanoparticles with ion-leaking properties disrupt intracellular ROS and iron homeostasis to induce ferroptosis

“…The third interesting finding in the current study is that ZnO NPs-induced dysregulation of iron homeostasis partially due to dissolved Zn 2+ . Although Zn 2+ is an inert cation and does not undergo a redox reaction, Zn 2+ overload is closely related to ROS and subsequently mitochondrial injuries 47,48 . The aberrant homeostasis of transition metal ions, e.g., Fe 2+ /Fe 3+ , Zn 2+ , and Ca 2+ , plays important roles in the pathogenesis of various diseases.…”