Neuroprotective Effect of Myxobacterial Extracts on Quinolinic Acid-Induced Toxicity in Primary Human Neurons
Quinolinic acid (QUIN) is a neurotoxin, gliotoxin, and proinflammatory molecule involved in the pathogenesis of several neurological diseases. Myxobacteria have been known as a rich source of secondary metabolites with diverse structures and mode of actions. In this study, we examined the potential neuroprotective effects of myxobacterial extracts on QUIN-induced excitotoxicity in primary human neurons. For this purpose, primary cultures of human neurons were pre-incubated with myxobacterial extracts and subsequently treated with QUIN at a pathophysiological concentration of 550 nM. The results showed that some myxobacterial extracts can significantly attenuate formation of reactive oxygen species (ROS), nitric oxide (NO) production, and extracellular lactate dehydrogenase (LDH) activity of human neurons. Moreover, myxobacterial extracts were also able to reduce neuronal nitric oxide synthase (nNOS) activity. Some extracts prevented cell death by reducing the activation of poly (ADP-ribose) polymerase (PARP1) by QUIN, therefore by maintaining NAD+ levels. In addition, myxobacterial extracts ameliorated oxidative stress by increasing the intracellular levels of glutathione after treatment with QUIN. The results showed that extracts of Stigmatella sp. UTMC 4072 and Archangium sp. UTMC 4070 and were the most effective in reducing QUIN-induced excitotoxicity in primary human neurons. Due to their antioxidative activity, myxobacterial extracts represent an underexplored source of potential new drugs for the treatment of neurodegenerative diseases.
KeywordsMyxobacteria Natural products Oxidative stress Anti-inflammation activity Quinolinic acid
Neuronal nitric oxide synthase
Poly (ADP-ribose) polymerase
Reactive nitrogen species
Reactive oxygen species
Ms. Mona Dehhaghi and Dr. Fatemeh Mohammadipanah are funded by the University of Tehran. Dr. Braidy is funded by the Australian Research Council, and Prof Guillemin is funded by the Australian Research Council, the National Health and Medical Research Council, the MND and Me Foundation, and Macquarie University.
Compliance with Ethical Standards
Approval for this study was obtained from the Human Research Ethics Committee of Macquarie University (#5201200411). This work has been performed in compliance with Ethical Standards.
Written informed consent was obtained from the participants.
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