Neuroprotective effect of myxobacterial extracts on quinolinic acid-induced toxicity in primary human neurons

Mona Dehhaghi, Vanessa Tan, Benjamin Heng, Nady Braidy, Fatemeh Mohammadipanah, Gilles J. Guillemin

Research output: Contribution to journalArticleResearchpeer-review

Abstract

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.

LanguageEnglish
Pages281-290
Number of pages10
JournalNeurotoxicity Research
Volume35
Issue number2
Early online date28 Sep 2018
DOIs
Publication statusPublished - Feb 2019

Fingerprint

Quinolinic Acid
Neuroprotective Agents
Neurons
Toxicity
Stigmatella
Gliotoxin
Myxococcales
Neurodegenerative diseases
Nitric Oxide Synthase Type I
Oxidative stress
Poly(ADP-ribose) Polymerases
Neurotoxins
Cell death
Metabolites
L-Lactate Dehydrogenase
Human Activities
Neurodegenerative Diseases
NAD
Glutathione
Reactive Oxygen Species

Keywords

  • Anti-inflammation activity
  • Myxobacteria
  • Natural products
  • Oxidative stress
  • Quinolinic acid

Cite this

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title = "Neuroprotective effect of myxobacterial extracts on quinolinic acid-induced toxicity in primary human neurons",
abstract = "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.",
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Neuroprotective effect of myxobacterial extracts on quinolinic acid-induced toxicity in primary human neurons. / Dehhaghi, Mona; Tan, Vanessa; Heng, Benjamin; Braidy, Nady; Mohammadipanah, Fatemeh; Guillemin, Gilles J.

In: Neurotoxicity Research, Vol. 35, No. 2, 02.2019, p. 281-290.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Heng,Benjamin

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