Kynurenines in Parkinson’s disease: therapeutic perspectives

Abstract

Parkinson's disease (PD) is a chronic progressive neurodegenerative disorder the pathomechanism of which is not yet fully known. With regard to the molecular mechanism of development of the disease, oxidative stress/mitochondrial impairment, glutamate excitotoxicity and neuroinflammation are certainly involved. Alterations in the kynurenine pathway, the main pathway of the tryptophan metabolism, can contribute to the complex pathomechanism. There are several possibilities for therapeutic intervention involving targeting of this altered metabolic route. The development of synthetic molecules that would shift the altered balance towards the achievement of neuroprotective effects would be of great promise for future clinical studies on PD.

Excitotoxins, Mitochondrial and Redox Disturbances in Multiple Sclerosis

“…There are attempts to use KYNA analogues to treat neurodegenerative disorders [72,76,176,177,178,179,180]. The structural KYNA analogue quinoline carboxamide (laquinimod) slowed the progression of MS and the annual relapse rate in a phase 3 study [71].…”

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“…Numerous data support the role of kynurenines in neurological diseases, including PD (Bohár et al 2015;Majláth et al 2016b;Klivényi et al 2004;Vécsei et al 2013;Zádori et al 2012b). One of the most important compounds of this system is kynurenic acid (KYNA) (Sas et al 2007).…”

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“…Parkinson’s disease (PD) is a progressive, chronic, neurodegenerative disease characterized by rigidity, tremor, bradykinesia and postural instability secondary to dopaminergic deficit in the nigrostriatal system 1–3. Currently, disease-modifying therapies are not available, and levodopa (LD) treatment remains the gold standard for controlling motor symptoms of the disease 4–7.…”