Quinolinic Acid - Treatment Focus

Treatment Focus

Reduction of the excitotoxic effects of quinolinic acid is the subject of on-going research. NMDAr antagonists have been shown to provide protection to motor neurons from excitotoxicity resulting from quinolinic acid production. Kyurenic acid, another product of the kyurenine pathway acts as an NMDA receptor antagonist.

Kyurenic acid thus acts as a neuroprotectant, by reducing the dangerous over-activation of the NMDA receptors. Manipulation of the kyurenine pathway away from quinolinic acid and towards kyurenic acid is therefore a major therapeutic focus. Nicotinylalanine has been shown to be an inhibitor of kynurenine hydroxylase which results in a decreased production of quinolinic acid, thus favoring kyurenic acid production. This change in balance has the potential to reduce hyperexcitability, and thus excitotoxic damage produced from elevated levels of quinolinic acid. Therapeutic efforts are also focusing on antioxidants which have been shown to provide protection against the pro-oxidant properties of quinolinic acid.

Norharmane suppresses the production of quinolinic acid, 3-hydroxykynurenine and nitric oxide synthase, thereby acting as a neuroprotectant. Natural phenols such as catechin hydrate, curcumin and epigallocatechin gallate reduce the neurotoxicity of quinolinic acid, via anti-oxidant and possibly calcium influx mechanisms. COX-2 inhibitors, such as licofelone have also demonstrated protective properties against the neurotoxic effects of quinolinic acid. COX-2 is upregulated in many neurotoxic disorders and is associated with increased ROS production. Inhibitors have demonstrated some evidence of efficacy in mental health disorders such as major depressive disorder, schizophrenia and Huntington's disease.