The kynurenine pathway (KP) and one of its end-products, the excitotoxin quinolinic acid (QUIN), are involved in the pathogenesis of several major neuroinflammatory brain diseases. In the last decade, the KP has emerged as a key regulator of the immune response. As humans and macaques share a very similar genetic makeup, studies involving central and systemic immune activation in mice, macaques and gerbils were able to replicate some clinical observations in patients with various neuropathological conditions. A relevant animal model to study KP metabolism is now needed to assess whether intervention in this pathway may improve the outcome of such diseases.

Gilles J. Guillemin, of the University of New South Wales, Sydney, Australia, describes the simian model as a relevant model to study the human cellular KP metabolism in his recent International Journal of Tryptophan Research article Characterization of the Kynurenine Pathway and Quinolinic Acid Production in Macaque Macrophages. Read on to find out more about this research:

How did you become interested in studying the kynurenine pathway and quinolinic acid production in macaque macrophages?

The kynurenine pathway profile is different between species especially in rodents, which represent the one of the most common animal models used to study human diseases.  So, due to their genetic similarity with human (both primates), it was important to characterize the simian kynurenine pathway to validate the primate model as the most relevant.

What was previously known about the involvement of kynurenine pathway and excitotoxin quinolinic acid in the pathogenesis of several major neuroinflammatory brain diseases?  How has your work in this area advanced understanding of it?

My group has been studying the involvement of the kynurenine pathway and the effects of the neurotoxin quinolinic acid in neuroinflammatory diseases for more than 15 years. We have shown that the kynurenine pathway and quinolinic acid are key players in many diseases including HIV-1 infection, Alzheimer’s disease, multiple sclerosis, amyotrophic lateral sclerosis, brain tumours, depression, suicide, autism….

What do regard as being the most important aspect of the results of your research?

Translational research: identifying prognostic markers for multiple sclerosis and now working on the development of new therapeutic strategies targeting the kynurenine pathway for neurodegenerative diseases.

What was the greatest difficulty you encountered in studying the KP and QUIN involvement in the pathogenesis of neuroinflammatory brain diseases?

We can’t really use “classical” animal models (rodents), as the kynurenine pathway is different between species. We have to look at larger animal models and genetically closer to human such as pig and monkeys.

To read more about Dr Guillemin’s experience in the field please visit his website or the Neurotoxicity Society webpage. The paper Characterization of the Kynurenine Pathway and Quinolinic Acid Production in Macaque Macrophages is freely available to download and share.

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