Phytochemical treatments target kynurenine pathway induced oxidative stress

Figures & data

Table 1. An overview of neurological disorders focusing on the main affected regions and the link to oxidative stress, increased glutamate levels cause excitotoxicity and may be triggered by quinolinic acid.

Neurological disease	Symptoms	Affected region	Role of oxidative stress	References
Amyotrophic Lateral Sclerosis	Progressive muscle weakness leading to paralysis	Central nervous system (brain stem, spine, cortex) – motor neurons	Mutations in superoxide dismutase 1 sensitizing motor neurons to excitotoxicity, lipid peroxidation, damage to astrocytes and microglia, and inflammation	[2,3]
Multiple Sclerosis	Muscle weakness, shaking	Loss of myelin sheath in the central nervous system	Inflammation	[3]
Huntington’s Disease	Impairment of motor, cognitive, and behavioural function	Central nervous system – cortex, striatum	Inflammation, lipid peroxidation	[3]
Parkinson’s Disease	Muscle weakness, resting tremor, postural instability	Substantia nigra – dopaminergic neurons	Interferes with dopamine metabolism; ROS cause neuron death	[3,4]
Alzheimer’s Disease	Impaired memory and cognitive functions	Amyloid beta plaques and tau protein accumulation in the central nervous system notably the hippocampus	Involved in toxicity associated with amyloid beta plaques, inflammation response of microglia, and lipid peroxidation	[3,5,6]

ROS: reactive oxygen species [2–6].

Figure 1. The kynurenine pathway of tryptophan metabolism. Tryptophan is transported into the brain by the l-amino acid transporter and converted by indole amine dioxygenases (IDO), rate limiting step, into formylkynurenine and then by kynurenine formamidase into kynurenine. Kynurenine can then be either converted into 3-hydroxykynurenine by kynurenine hydroxylase then into 3-hydroxythranillic acid. Once 3-hydroxythranillic acid is produced it can then be converted to quinolinic acid spontaneously or picolinic acid by picolinic carboxylase. 3-hydroxylkynurenine can be converted to xanthurenic acid and kynurenine into kynurenic acid by kynurenine aminotransferases. NP: neuroprotective; NT: neurotoxic [2,6,22,25,38].

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