Sathyasaikumar V. Korrapati, PhD

University of Madras, Chennai, India, B.Sc. Zoology (1995)

University of Madras, Chennai, India, M.Sc. Zoology (1997)

University of Madras, Chennai, India, MPhil. Zoology (1998)

University of Hyderabad, Hyderabad, India, Ph.D.  Animal Sciences (2007)

I am a basic neuroscientist and have been working on the kynurenine pathway metabolism for the last 15+ years. My focus is on impairment of kynurenine pathway enzymes in brain diseases. For example, elevated concentrations of neurotoxic metabolites of the kynurenine pathway of tryptophan degradation may play a causative role in Huntington’s disease (HD). The brain levels of 3-hydroxykynurenine (3-HK) and quinolinic acid were found to be increased in both HD and several mouse models of the disease. Since the toxic metabolites are elevated in Huntington’s disease, I sought to find the reasons behind this increase. I showed that kynurenine 3-monoygenase and kynureninase were affected in this disease in the R6/2 mice model. The finding is extremely important to the field as it facilitates developing new drugs to target these enzymes.

I then shifted my focus to schizophrenia (an important severe mental disease) as our center where I work is focused on schizophrenia research. I pioneered some of the key discoveries regarding the kynurenine pathway metabolism in this disease. I showed that kynurenine 3-monooxygenase is decreased in the prefrontal cortex area of post-mortem brains in people with schizophrenia and the reason for elevated levels of kynurenic acid in these patients. Kynurenic acid is an antagonist of two receptors that are closely linked to cognitive phenomena and psychosis, ie, the alpha7 nicotinic acetylcholine receptor and the N-methyl-D-aspartate receptor. By reducing the function of one or both of these receptors, increases in brain kynurenic acid levels might therefore cause hyponicotinergic and hypoglutamatergic conditions. Therefore, it is conceivable that increased levels of kynurenic acid may play a role in the pathophysiology of schizophrenia. Targeting, either the kynurenine 3-monooxygenase enzyme (by activators) or kynurenine aminotransferase II (by inhibitors) could be helpful in treating the people with schizophrenia to improve some of the cognitive and behavioral deficits observed in schizophrenia like working memory and attention deficits.

Kynurenine Pathway Metabolism, Neurodegeneration, Schizophrenia, Cognition

• Sathyasaikumar KV, Stachowski EK, Wonodi I, Roberts RC, Rassoulpour A, McMahon RP, Schwarcz Impaired kynurenine pathway metabolism in the prefrontal cortex of individuals with schizophrenia. Schizophr Bull. 2011:37:1147-1156.
• Zwilling D, Huang SY, Sathyasaikumar KV, Notarangelo FM, Guidetti P, Wu HQ, Lee J, Truong J, Andrews-Zwilling Y, Hsieh EW, Louie JY, Wu T, Scearce-Levie K, Patrick C, Adame A, Giorgini F, Moussaoui S, Laue G, Rassoulpour A, Flik G, Huang Y, Muchowski JM, Masliah E, Schwarcz R, Muchowski PJ. Kynurenine 3- monoxygenase inhibition in blood ameliorates neurodegeneration. Cell. 2011:145:863- 874.
• Campesan S, Green EW, Breda C, Sathyasaikumar KV, Muchowski PJ, Schwarcz R, Kyriacou CP, Giorgini F. The kynurenine pathway modulates neurodegeneration in a Drosophila model of Huntington's disease. Curr Biol. 2011:21:961-966
• Giorgini F, Huang SY, Sathyasaikumar KV, Notarangelo FM, Thomas MA, Tararina M, Wu HQ, Schwarcz R, Muchowski PJ. Targeted deletion of Kynurenine 3- monooxygenase in mice: A new tool for studying kynurenine pathway metabolism in periphery and brain. JBC. 2013: 288:36554-36566.
• Sathyasaikumar KV, Pérez de la Cruz V, Pineda B, Vázquez Cervantes GI, Ramírez Ortega D, Donley DW, Severson PL, West BL, Giorgini F, Fox JH, Schwarcz R. Cellular localization of kynurenine 3-monooxygenase in the brain: challenging the dogma. Antioxidants. 2022:11:315