538765.fig.002a
(a)
538765.fig.002b
(b)
Figure 2: (a) Schematic diagram of kynurenine pathway. TDO—tryptophan 2,3-dioxygenase, IDO—indoleamine 2,3-dioxygenase, KAT—kynurenine aminotransferase, KZ—kynureninase, HK—kynurenine 3-hydroxylase, HAO—3-hydroxyanthranilate-3,4-dioxygenase, PC—picolinic carboxylase, NC—nonenzymic cyclization. Details are given in the text. (b) Schematic representation of QUIN toxicity in motor neurons. Due to presence of large number of activated glial cells in ALS, there is release of large amount of QUIN into the microenvironment, which can then result in excitotoxicity in motor neurons via NMDA receptors, or it can also be taken up in large quantities by motor neurons. Ultimately, excitotoxicity and the accumulation of QUIN contribute to the demise of motor neurons.