The Involvement of Kynurenine Pathway in Neurodegenerative Diseases

Feigin, V.L.; Abajobir, A.A.; Abate, K.H.; Abd-Allah, F.; Abdulle, A.M.; Abera, S.F.; Abyu, G.Y.; Ahmed, M.B.; Aichour, A.N.; Aichour, I.; Aichour, M.T.E.; Akinyemi, R.O.; Alabed, S.; Al-Raddadi, R.; Alvis-Guzman, N.; Amare, A.T.; Ansari, H.; Anwari, P.; Ärnlöv, J.; Asayesh, H.; Asgedom, S.W.; Atey, T.M.; Avila-Burgos, L.; Frinel, E.; Avokpaho, G.A.; Azarpazhooh, M.R.; Barac, A.; Barboza, M.; Barker-Collo, S.L.; Bärnighausen, T.; Bedi, N.; Beghi, E.; Bennett, D.A.; Bensenor, I.M.; Berhane, A.; Betsu, B.D.; Bhaumik, S.; Birlik, S.M.; Biryukov, S.; Boneya, D.J.; Bulto, L.N.B.; Carabin, H.; Casey, D.; Castañeda-Orjuela, C.A.; Catalá-López, F.; Chen, H.; Chitheer, A.A.; Chowdhury, R.; Christensen, H.; Dandona, L.; Dandona, R.; de Veber, G.A.; Dharmaratne, S.D.; Do, H.P.; Dokova, K.; Dorsey, E.R.; Ellenbogen, R.G.; Eskandarieh, S.; Farvid, M.S.; Fereshtehnejad, S-M.; Fischer, F.; Foreman, K.J.; Geleijnse, J.M.; Gillum, R.F.; Giussani, G.; Goldberg, E.M.; Gona, P.N.; Goulart, A.C.; Gugnani, H.C.; Gupta, R.; Hachinski, V.; Gupta, R.; Hamadeh, R.R.; Hambisa, M.; Hankey, G.J.; Hareri, H.A.; Havmoeller, R.; Hay, S.I.; Heydarpour, P.; Hotez, P.J.; Jakovljevic, M.M.B.; Javanbakht, M.; Jeemon, P.; Jonas, J.B.; Kalkonde, Y.; Kandel, A.; Karch, A.; Kasaeian, A.; Kastor, A.; Keiyoro, P.N.; Khader, Y.S.; Khalil, I.A.; Khan, E.A.; Khang, Y-H.; Tawfih, A.; Khoja, A.; Khubchandani, J.; Kulkarni, C.; Kim, D.; Kim, Y.J.; Kivimaki, M.; Kokubo, Y.; Kosen, S.; Kravchenko, M.; Krishnamurthi, R.V.; Defo, B.K.; Kumar, G.A.; Kumar, R.; Kyu, H.H.; Larsson, A.; Lavados, P.M.; Li, Y.; Liang, X.; Liben, M.L.; Lo, W.D.; Logroscino, G.; Lotufo, P.A.; Loy, C.T.; Mackay, M.T.; El Razek, H.M.A.; El Razek, M.M.A.; Majeed, A.; Malekzadeh, R.; Manhertz, T.; Mantovani, L.G.; Massano, J.; Mazidi, M.; McAlinden, C.; Mehata, S.; Mehndiratta, M.M.; Memish, Z.A.; Mendoza, W.; Mengistie, M.A.; Mensah, G.A.; Meretoja, A.; Mezgebe, H.B.; Miller, T.R.; Mishra, S.R.; Ibrahim, N.M.; Mohammadi, A.; Mohammed, K.E.; Mohammed, S.; Mokdad, A.H.; Moradi-Lakeh, M.; Velasquez, I.M.; Musa, K.I.; Naghavi, M.; Ngunjiri, J.W.; Nguyen, C.T.; Nguyen, G.; Le Nguyen, Q.; Nguyen, T.H.; Nichols, E.; Ningrum, D.N.A.; Nong, V.M.; Norrving, B.; Noubiap, J.J.N.; Ogbo, F.A.; Owolabi, M.O.; Pandian, J.D.; Parmar, P.G.; Pereira, D.M.; Petzold, M.; Phillips, M.R.; Piradov, M.A.; Poulton, R.G.; Pourmalek, F.; Qorbani, M.; Rafay, A.; Rahman, M.; Rahman, M.H.U.; Rai, R.K.; Rajsic, S.; Ranta, A.; Rawaf, S.; Renzaho, A.M.N.; Rezai, M.S.; Roth, G.A.; Roshandel, G.; Rubagotti, E.; Sachdev, P.; Safiri, S.; Sahathevan, R.; Sahraian, M.A.; Samy, A.M.; Santalucia, P.; Santos, I.S.; Sartorius, B.; Satpathy, M.; Sawhney, M.; Saylan, M.I.; Sepanlou, S.G.; Shaikh, M.A.; Shakir, R.; Shamsizadeh, M.; Sheth, K.N.; Shigematsu, M.; Shoman, H.; Silva, D.A.S.; Smith, M.; Sobngwi, E.; Sposato, L.A.; Stanaway, J.D.; Stein, D.J.; Steiner, T.J.; Stovner, L.J.; Abdulkader, R.S.; E.I., Szoeke C.; Tabarés-Seisdedos, R.; Tanne, D.; Theadom, A.M.; Thrift, A.G.; Tirschwell, D.L.; Topor-Madry, R.; Tran, B.X.; Truelsen, T.; Tuem, K.B.; Ukwaja, K.N.; Uthman, O.A.; Varakin, Y.Y.; Vasankari, T.; Venketasubramanian, N.; Vlassov, V.V.; Wadilo, F.; Wakayo, T.; Wallin, M.T.; Weiderpass, E.; Westerman, R.; Wijeratne, T.; Wiysonge, C.S.; Woldu, M.A.; Wolfe, C.D.A.; Xavier, D.; Xu, G.; Yano, Y.; Yimam, H.H.; Yonemoto, N.; Yu, C.; Zaidi, Z.; El Sayed Zaki, M.; Zunt, J.R.; Murray, C.J.L.; Vos, T. Group GBDNDC. Global, regional, and national burden of neurological disorders during 1990–2015: A systematic analysis for the Global Burden of Disease Study 2015. Lancet Neurol., 2017, 16(11), 877-897.
[http://dx.doi.org/10.1016/S1474-4422(17)30299-5] [PMID: 28931491]

Tanaka, M.; Toldi, J.; Vécsei, L. Exploring the etiological links behind neurodegenerative diseases: Inflammatory cytokines and bioactive kynurenines. Int. J. Mol. Sci., 2020, 21(7), 2431.
[http://dx.doi.org/10.3390/ijms21072431] [PMID: 32244523]

Marras, C.; Beck, J.C.; Bower, J.H.; Roberts, E.; Ritz, B.; Ross, G.W.; Abbott, R.D.; Savica, R.; Van Den Eeden, S.K.; Willis, A.W.; Tanner, C.M. Prevalence of Parkinson’s disease across North America. NPJ Parkinsons Dis., 2018, 4(1), 21.
[http://dx.doi.org/10.1038/s41531-018-0058-0] [PMID: 30003140]

Alzheimer's A, 2017 Alzheimer’s disease facts and figures. Alzheimers Dement., 2017, 13(4), 325-373.
[http://dx.doi.org/10.1016/j.jalz.2017.02.001]

Scheltens, P.; Blennow, K.; Breteler, M.M.B.; de Strooper, B.; Frisoni, G.B.; Salloway, S.; Van der Flier, W.M. Alzheimer’s disease. Lancet, 2016, 388(10043), 505-517.
[http://dx.doi.org/10.1016/S0140-6736(15)01124-1] [PMID: 26921134]

Nichols, E.; Steinmetz, J.D.; Vollset, S.E.; Fukutaki, K.; Chalek, J.; Abd-Allah, F.; Abdoli, A.; Abualhasan, A.; Abu-Gharbieh, E.; Akram, T.T.; Al Hamad, H.; Alahdab, F.; Alanezi, F.M.; Alipour, V.; Almustanyir, S.; Amu, H.; Ansari, I.; Arabloo, J.; Ashraf, T.; Astell-Burt, T.; Ayano, G.; Ayuso-Mateos, J.L.; Baig, A.A.; Barnett, A.; Barrow, A.; Baune, B.T.; Béjot, Y.; Bezabhe, W.M.M.; Bezabih, Y.M.; Bhagavathula, A.S.; Bhaskar, S.; Bhattacharyya, K.; Bijani, A.; Biswas, A.; Bolla, S.R.; Boloor, A.; Brayne, C.; Brenner, H.; Burkart, K.; Burns, R.A.; Cámera, L.A.; Cao, C.; Carvalho, F.; Castro-de-Araujo, L.F.S.; Catalá-López, F.; Cerin, E.; Chavan, P.P.; Cherbuin, N.; Chu, D-T.; Costa, V.M.; Couto, R.A.S.; Dadras, O.; Dai, X.; Dandona, L.; Dandona, R.; De la Cruz-Góngora, V.; Dhamnetiya, D.; Dias da Silva, D.; Diaz, D.; Douiri, A.; Edvardsson, D.; Ekholuenetale, M.; El Sayed, I.; El-Jaafary, S.I.; Eskandari, K.; Eskandarieh, S.; Esmaeilnejad, S.; Fares, J.; Faro, A.; Farooque, U.; Feigin, V.L.; Feng, X.; Fereshtehnejad, S-M.; Fernandes, E.; Ferrara, P.; Filip, I.; Fillit, H.; Fischer, F.; Gaidhane, S.; Galluzzo, L.; Ghashghaee, A.; Ghith, N.; Gialluisi, A.; Gilani, S.A.; Glavan, I-R.; Gnedovskaya, E.V.; Golechha, M.; Gupta, R.; Gupta, V.B.; Gupta, V.K.; Haider, M.R.; Hall, B.J.; Hamidi, S.; Hanif, A.; Hankey, G.J.; Haque, S.; Hartono, R.K.; Hasaballah, A.I.; Hasan, M.T.; Hassan, A.; Hay, S.I.; Hayat, K.; Hegazy, M.I.; Heidari, G.; Heidari-Soureshjani, R.; Herteliu, C.; Househ, M.; Hussain, R.; Hwang, B-F.; Iacoviello, L.; Iavicoli, I.; Ilesanmi, O.S.; Ilic, I.M.; Ilic, M.D.; Irvani, S.S.N.; Iso, H.; Iwagami, M.; Jabbarinejad, R.; Jacob, L.; Jain, V.; Jayapal, S.K.; Jayawardena, R.; Jha, R.P.; Jonas, J.B.; Joseph, N.; Kalani, R.; Kandel, A.; Kandel, H.; Karch, A.; Kasa, A.S.; Kassie, G.M.; Keshavarz, P.; Khan, M.A.B.; Khatib, M.N.; Khoja, T.A.M.; Khubchandani, J.; Kim, M.S.; Kim, Y.J.; Kisa, A.; Kisa, S.; Kivimäki, M.; Koroshetz, W.J.; Koyanagi, A.; Kumar, G.A.; Kumar, M.; Lak, H.M.; Leonardi, M.; Li, B.; Lim, S.S.; Liu, X.; Liu, Y.; Logroscino, G.; Lorkowski, S.; Lucchetti, G.; Lutzky Saute, R.; Magnani, F.G.; Malik, A.A.; Massano, J.; Mehndiratta, M.M.; Menezes, R.G.; Meretoja, A.; Mohajer, B.; Mohamed Ibrahim, N.; Mohammad, Y.; Mohammed, A.; Mokdad, A.H.; Mondello, S.; Moni, M.A.A.; Moniruzzaman, M.; Mossie, T.B.; Nagel, G.; Naveed, M.; Nayak, V.C.; Neupane Kandel, S.; Nguyen, T.H.; Oancea, B.; Otstavnov, N.; Otstavnov, S.S.; Owolabi, M.O.; Panda-Jonas, S.; Pashazadeh Kan, F.; Pasovic, M.; Patel, U.K.; Pathak, M.; Peres, M.F.P.; Perianayagam, A.; Peterson, C.B.; Phillips, M.R.; Pinheiro, M.; Piradov, M.A.; Pond, C.D.; Potashman, M.H.; Pottoo, F.H.; Prada, S.I.; Radfar, A.; Raggi, A.; Rahim, F.; Rahman, M.; Ram, P.; Ranasinghe, P.; Rawaf, D.L.; Rawaf, S.; Rezaei, N.; Rezapour, A.; Robinson, S.R.; Romoli, M.; Roshandel, G.; Sahathevan, R.; Sahebkar, A.; Sahraian, M.A.; Sathian, B.; Sattin, D.; Sawhney, M.; Saylan, M.; Schiavolin, S.; Seylani, A.; Sha, F.; Shaikh, M.A.; Shaji, K.S.; Shannawaz, M.; Shetty, J.K.; Shigematsu, M.; Shin, J.I.; Shiri, R.; Silva, D.A.S.; Silva, J.P.; Silva, R.; Singh, J.A.; Skryabin, V.Y.; Skryabina, A.A.; Smith, A.E.; Soshnikov, S.; Spurlock, E.E.; Stein, D.J.; Sun, J.; Tabarés-Seisdedos, R.; Thakur, B.; Timalsina, B.; Tovani-Palone, M.R.; Tran, B.X.; Tsegaye, G.W.; Valadan Tahbaz, S.; Valdez, P.R.; Venketasubramanian, N.; Vlassov, V.; Vu, G.T.; Vu, L.G.; Wang, Y-P.; Wimo, A.; Winkler, A.S.; Yadav, L.; Yahyazadeh Jabbari, S.H.; Yamagishi, K.; Yang, L.; Yano, Y.; Yonemoto, N.; Yu, C.; Yunusa, I.; Zadey, S.; Zastrozhin, M.S.; Zastrozhina, A.; Zhang, Z-J.; Murray, C.J.L.; Vos, T. Collaborators GBDDF. Estimation of the global prevalence of dementia in 2019 and forecasted prevalence in 2050: An analysis for the Global Burden of Disease Study 2019. Lancet Public Health, 2022, 7(2), e105-e125.
[http://dx.doi.org/10.1016/S2468-2667(21)00249-8] [PMID: 34998485]

Dorsey, E.R.; Constantinescu, R.; Thompson, J.P.; Biglan, K.M.; Holloway, R.G.; Kieburtz, K.; Marshall, F.J.; Ravina, B.M.; Schifitto, G.; Siderowf, A.; Tanner, C.M. Projected number of people with Parkinson disease in the most populous nations, 2005 through 2030. Neurology, 2007, 68(5), 384-386.
[http://dx.doi.org/10.1212/01.wnl.0000247740.47667.03] [PMID: 17082464]

Pangalos, M.N.; Schechter, L.E.; Hurko, O. Drug development for CNS disorders: Strategies for balancing risk and reducing attrition. Nat. Rev. Drug Discov., 2007, 6(7), 521-532.
[http://dx.doi.org/10.1038/nrd2094] [PMID: 17599084]

Schwarcz, R.; Bruno, J.P.; Muchowski, P.J.; Wu, H.Q. Kynurenines in the mammalian brain: When physiology meets pathology. Nat. Rev. Neurosci., 2012, 13(7), 465-477.
[http://dx.doi.org/10.1038/nrn3257] [PMID: 22678511]

van der Goot, A.T.; Nollen, E.A.A. Tryptophan metabolism: Entering the field of aging and age-related pathologies. Trends Mol. Med., 2013, 19(6), 336-344.
[http://dx.doi.org/10.1016/j.molmed.2013.02.007] [PMID: 23562344]

Pertovaara, M.; Raitala, A.; Lehtimäki, T.; Karhunen, P.J.; Oja, S.S.; Jylhä, M.; Hervonen, A.; Hurme, M. Indoleamine 2,3-dioxygenase activity in nonagenarians is markedly increased and predicts mortality. Mech. Ageing Dev., 2006, 127(5), 497-499.
[http://dx.doi.org/10.1016/j.mad.2006.01.020] [PMID: 16513157]

Kim, B.J.; Hamrick, M.W.; Yoo, H.J.; Lee, S.H.; Kim, S.J.; Koh, J.M.; Isales, C.M. The detrimental effects of kynurenine, a tryptophan metabolite, on human bone metabolism. J. Clin. Endocrinol. Metab., 2019, 104(6), 2334-2342.
[http://dx.doi.org/10.1210/jc.2018-02481] [PMID: 30715395]

Zuo, H.; Ueland, P.M.; Ulvik, A.; Eussen, S.J.P.M.; Vollset, S.E.; Nygård, O.; Midttun, Ø.; Theofylaktopoulou, D.; Meyer, K.; Tell, G.S. Plasma biomarkers of inflammation, the kynurenine pathway, and risks of all-cause, cancer, and cardiovascular disease mortality. Am. J. Epidemiol., 2016, 183(4), 249-258.
[http://dx.doi.org/10.1093/aje/kwv242] [PMID: 26823439]

Franceschi, C.; Garagnani, P.; Parini, P.; Giuliani, C.; Santoro, A. Inflammaging: A new immune–metabolic viewpoint for age-related diseases. Nat. Rev. Endocrinol., 2018, 14(10), 576-590.
[http://dx.doi.org/10.1038/s41574-018-0059-4] [PMID: 30046148]

Le Floc’h, N.; Otten, W.; Merlot, E. Tryptophan metabolism, from nutrition to potential therapeutic applications. Amino Acids, 2011, 41(5), 1195-1205.
[http://dx.doi.org/10.1007/s00726-010-0752-7] [PMID: 20872026]

Rocha, N.P.; de Miranda, A.S.; Teixeira, A.L. Insights into neuroinflammation in Parkinson’s Disease: From biomarkers to anti-inflammatory based therapies. BioMed Res. Int., 2015, 2015, 1-12.
[http://dx.doi.org/10.1155/2015/628192] [PMID: 26295044]

Valadão, P.A.C.; Santos, K.B.S.; Ferreira e Vieira, T.H.; Macedo e Cordeiro, T.; Teixeira, A.L.; Guatimosim, C.; de Miranda, A.S. Inflammation in Huntington’s disease: A few new twists on an old tale. J. Neuroimmunol., 2020, 348, 577380.
[http://dx.doi.org/10.1016/j.jneuroim.2020.577380] [PMID: 32896821]

Bauer, M.E.; Teixeira, A.L. Inflammation in psychiatric disorders: what comes first? Ann. N. Y. Acad. Sci., 2019, 1437(1), 57-67.
[http://dx.doi.org/10.1111/nyas.13712] [PMID: 29752710]

Mészáros, Á.; Molnár, K.; Nógrádi, B.; Hernádi, Z.; Nyúl-Tóth, Á.; Wilhelm, I.; Krizbai, I.A. Neurovascular inflammaging in health and disease. Cells, 2020, 9(7), 1614.
[http://dx.doi.org/10.3390/cells9071614] [PMID: 32635451]

Franceschi, C.; Garagnani, P.; Vitale, G.; Capri, M.; Salvioli, S. Inflammaging and ‘Garb-aging’. Trends Endocrinol. Metab., 2017, 28(3), 199-212.
[http://dx.doi.org/10.1016/j.tem.2016.09.005] [PMID: 27789101]

Colpo, G.D.; Venna, V.R.; McCullough, L.D.; Teixeira, A.L. Systematic review on the involvement of the kynurenine pathway in stroke: Pre-clinical and clinical evidence. Front. Neurol., 2019, 10, 778.
[http://dx.doi.org/10.3389/fneur.2019.00778] [PMID: 31379727]

Sathyasaikumar, K.V.; Tararina, M.; Wu, H.Q.; Neale, S.A.; Weisz, F.; Salt, T.E.; Schwarcz, R. Xanthurenic acid formation from 3-hydroxykynurenine in the mammalian brain: Neurochemical characterization and physiological effects. Neuroscience, 2017, 367, 85-97.
[http://dx.doi.org/10.1016/j.neuroscience.2017.10.006] [PMID: 29031603]

Baranyi, A.; Amouzadeh-Ghadikolai, O.; Lewinski, D.; Breitenecker, R.J.; Stojakovic, T.; März, W.; Robier, C.; Rothenhäusler, H.B.; Mangge, H.; Meinitzer, A. Beta-trace protein as a new non-invasive immunological marker for quinolinic acid-induced impaired blood-brain barrier integrity. Sci. Rep., 2017, 7(1), 43642.
[http://dx.doi.org/10.1038/srep43642] [PMID: 28276430]

Hernandez-Martinez, J.M.; Forrest, C.M.; Darlington, L.G.; Smith, R.A.; Stone, T.W. Quinolinic acid induces neuritogenesis in SH-SY5Y neuroblastoma cells independently of NMDA receptor activation. Eur. J. Neurosci., 2017, 45(5), 700-711.
[http://dx.doi.org/10.1111/ejn.13499] [PMID: 27973747]

Fazio, F.; Lionetto, L.; Curto, M.; Iacovelli, L.; Cavallari, M.; Zappulla, C.; Ulivieri, M.; Napoletano, F.; Capi, M.; Corigliano, V.; Scaccianoce, S.; Caruso, A.; Miele, J.; De Fusco, A.; Di Menna, L.; Comparelli, A.; De Carolis, A.; Gradini, R.; Nisticò, R.; De Blasi, A.; Girardi, P.; Bruno, V.; Battaglia, G.; Nicoletti, F.; Simmaco, M. Xanthurenic acid activates mGlu2/3 metabotropic glutamate receptors and is a potential trait marker for schizophrenia. Sci. Rep., 2016, 5(1), 17799.
[http://dx.doi.org/10.1038/srep17799] [PMID: 26643205]

Fazio, F.; Zappulla, C.; Notartomaso, S.; Busceti, C.; Bessede, A.; Scarselli, P.; Vacca, C.; Gargaro, M.; Volpi, C.; Allegrucci, M.; Lionetto, L.; Simmaco, M.; Belladonna, M.L.; Nicoletti, F.; Fallarino, F. Cinnabarinic acid, an endogenous agonist of type-4 metabotropic glutamate receptor, suppresses experimental autoimmune encephalomyelitis in mice. Neuropharmacology, 2014, 81, 237-243.
[http://dx.doi.org/10.1016/j.neuropharm.2014.02.011] [PMID: 24565643]

Ulivieri, M. Wierońska, J.M.; Lionetto, L.; Martinello, K.; Cieslik, P.; Chocyk, A.; Curto, M.; Di Menna, L.; Iacovelli, L.; Traficante, A.; Liberatore, F.; Mascio, G.; Antenucci, N.; Giannino, G.; Vergassola, M.; Pittaluga, A.; Bruno, V.; Battaglia, G.; Fucile, S.; Simmaco, M.; Nicoletti, F.; Pilc, A.; Fazio, F. The trace kynurenine, cinnabarinic acid, displays potent antipsychotic-like activity in mice and its levels are reduced in the prefrontal cortex of individuals affected by schizophrenia. Schizophr. Bull., 2020, 46(6), 1471-1481.
[http://dx.doi.org/10.1093/schbul/sbaa074] [PMID: 32506121]

Fazio, F; Lionetto, L; Curto, M Cinnabarinic acid and xanthurenic acid: Two kynurenine metabolites that interact with metabotropic glutamate receptors. Neuropharmacol., 2017, 112(Pt B), 365-72.

Neale, S.A.; Copeland, C.S.; Uebele, V.N.; Thomson, F.J.; Salt, T.E. Modulation of hippocampal synaptic transmission by the kynurenine pathway member xanthurenic acid and other VGLUT inhibitors. Neuropsychopharmacol., 2013, 38(6), 1060-1067.
[http://dx.doi.org/10.1038/npp.2013.4] [PMID: 23303071]

Terry, N.; Margolis, K.G. Serotonergic mechanisms regulating the gi tract: experimental evidence and therapeutic relevance. Handb. Exp. Pharmacol., 2016, 239, 319-342.
[http://dx.doi.org/10.1007/164_2016_103] [PMID: 28035530]

Oishi, A.; Gbahou, F.; Jockers, R. Melatonin receptors, brain functions, and therapies. Handb. Clin. Neurol., 2021, 179, 345-356.
[http://dx.doi.org/10.1016/B978-0-12-819975-6.00022-4] [PMID: 34225974]

Rodríguez, J.J.; Noristani, H.N.; Verkhratsky, A. The serotonergic system in ageing and Alzheimer’s disease. Prog. Neurobiol., 2012, 99(1), 15-41.
[http://dx.doi.org/10.1016/j.pneurobio.2012.06.010] [PMID: 22766041]

Liu, R.Y.; Zhou, J.N.; van Heerikhuize, J.; Hofman, M.A.; Swaab, D.F. Decreased melatonin levels in postmortem cerebrospinal fluid in relation to aging, Alzheimer’s disease, and apolipoprotein E-epsilon4/4 genotype. J. Clin. Endocrinol. Metab., 1999, 84(1), 323-327.
[PMID: 9920102]

Behl, T.; Kaur, I.; Sehgal, A.; Singh, S.; Bhatia, S.; Al-Harrasi, A.; Zengin, G.; Bumbu, A.G.; Andronie-Cioara, F.L.; Nechifor, A.C.; Gitea, D.; Bungau, A.F.; Toma, M.M.; Bungau, S.G. The footprint of kynurenine pathway in neurodegeneration: Janus-faced role in Parkinson’s disorder and therapeutic implications. Int. J. Mol. Sci., 2021, 22(13), 6737.
[http://dx.doi.org/10.3390/ijms22136737] [PMID: 34201647]

Ferreira, S.T.; Clarke, J.R.; Bomfim, T.R.; De Felice, F.G. Inflammation, defective insulin signaling, and neuronal dysfunction in Alzheimer’s disease. Alzheimers Dement., 2014, 10(1S)(Suppl.), S76-S83.
[http://dx.doi.org/10.1016/j.jalz.2013.12.010] [PMID: 24529528]

Parker, A.; Fonseca, S.; Carding, S.R. Gut microbes and metabolites as modulators of blood-brain barrier integrity and brain health. Gut Microbes, 2020, 11(2), 135-157.
[http://dx.doi.org/10.1080/19490976.2019.1638722] [PMID: 31368397]

Kivipelto, M.; Mangialasche, F.; Ngandu, T. Lifestyle interventions to prevent cognitive impairment, dementia and Alzheimer disease. Nat. Rev. Neurol., 2018, 14(11), 653-666.
[http://dx.doi.org/10.1038/s41582-018-0070-3] [PMID: 30291317]

Sperling, R.; Mormino, E.; Johnson, K. The evolution of preclinical Alzheimer’s disease: Implications for prevention trials. Neuron, 2014, 84(3), 608-622.
[http://dx.doi.org/10.1016/j.neuron.2014.10.038] [PMID: 25442939]

Guillemin, G.J. Smythe, G.A.; Veas, L.A.; Takikawa, O.; Brew, B.J. Aβ1-42 induces production of quinolinic acid by human macrophages and microglia. Neuroreport, 2003, 14(18), 2311-2315.
[http://dx.doi.org/10.1097/00001756-200312190-00005] [PMID: 14663182]

Guillemin, G.J.; Brew, B.J.; Noonan, C.E.; Takikawa, O.; Cullen, K.M. Indoleamine 2,3 dioxygenase and quinolinic acid immunoreactivity in Alzheimer’s disease hippocampus. Neuropathol. Appl. Neurobiol., 2005, 31(4), 395-404.
[http://dx.doi.org/10.1111/j.1365-2990.2005.00655.x] [PMID: 16008823]

Wu, W.; Nicolazzo, J.A.; Wen, L.; Chung, R.; Stankovic, R.; Bao, S.S.; Lim, C.K.; Brew, B.J.; Cullen, K.M.; Guillemin, G.J. Expression of tryptophan 2,3-dioxygenase and production of kynurenine pathway metabolites in triple transgenic mice and human Alzheimer’s disease brain. PLoS One, 2013, 8(4), e59749.
[http://dx.doi.org/10.1371/journal.pone.0059749] [PMID: 23630570]

Bonda, D.J.; Mailankot, M.; Stone, J.G.; Garrett, M.R.; Staniszewska, M.; Castellani, R.J.; Siedlak, S.L.; Zhu, X.; Lee, H.; Perry, G.; Nagaraj, R.H.; Smith, M.A. Indoleamine 2,3-dioxygenase and 3-hydroxykynurenine modifications are found in the neuropathology of Alzheimer’s disease. Redox Rep., 2010, 15(4), 161-168.
[http://dx.doi.org/10.1179/174329210X12650506623645] [PMID: 20663292]

van der Velpen, V.; Teav, T.; Gallart-Ayala, H.; Mehl, F.; Konz, I.; Clark, C.; Oikonomidi, A.; Peyratout, G.; Henry, H.; Delorenzi, M.; Ivanisevic, J.; Popp, J. Systemic and central nervous system metabolic alterations in Alzheimer’s disease. Alzheimers Res. Ther., 2019, 11(1), 93.
[http://dx.doi.org/10.1186/s13195-019-0551-7] [PMID: 31779690]

González-Sánchez, M.; Jiménez, J.; Narváez, A.; Antequera, D.; Llamas-Velasco, S.; Martín, A.H.S.; Molina Arjona, J.A.; López de Munain, A.; Lleó Bisa, A.; Marco, M.P.; Rodríguez-Núñez, M.; Pérez-Martínez, D.A.; Villarejo-Galende, A.; Bartolome, F.; Domínguez, E.; Carro, E. Kynurenic acid levels are increased in the CSF of Alzheimer’s Disease patients. Biomolecules, 2020, 10(4), 571.
[http://dx.doi.org/10.3390/biom10040571] [PMID: 32276479]

Jacobs, K.R.; Lim, C.K.; Blennow, K.; Zetterberg, H.; Chatterjee, P.; Martins, R.N.; Brew, B.J.; Guillemin, G.J.; Lovejoy, D.B. Correlation between plasma and CSF concentrations of kynurenine pathway metabolites in Alzheimer’s disease and relationship to amyloid-β and tau. Neurobiol. Aging, 2019, 80, 11-20.
[http://dx.doi.org/10.1016/j.neurobiolaging.2019.03.015] [PMID: 31055163]

Karikari, T.K.; Pascoal, T.A.; Ashton, N.J.; Janelidze, S.; Benedet, A.L.; Rodriguez, J.L.; Chamoun, M.; Savard, M.; Kang, M.S.; Therriault, J.; Schöll, M.; Massarweh, G.; Soucy, J.P.; Höglund, K.; Brinkmalm, G.; Mattsson, N.; Palmqvist, S.; Gauthier, S.; Stomrud, E.; Zetterberg, H.; Hansson, O.; Rosa-Neto, P.; Blennow, K. Blood phosphorylated tau 181 as a biomarker for Alzheimer’s disease: A diagnostic performance and prediction modelling study using data from four prospective cohorts. Lancet Neurol., 2020, 19(5), 422-433.
[http://dx.doi.org/10.1016/S1474-4422(20)30071-5] [PMID: 32333900]

Török, N.; Tanaka, M.; Vécsei, L. Searching for peripheral biomarkers in neurodegenerative diseases: The tryptophan-kynurenine metabolic pathway. Int. J. Mol. Sci., 2020, 21(24), 9338.
[http://dx.doi.org/10.3390/ijms21249338] [PMID: 33302404]

Skorobogatov, K.; De Picker, L.; Verkerk, R.; Coppens, V.; Leboyer, M.; Müller, N.; Morrens, M. Brain versus blood: A systematic review on the concordance between peripheral and central kynurenine pathway measures in psychiatric disorders. Front. Immunol., 2021, 12, 716980.
[http://dx.doi.org/10.3389/fimmu.2021.716980] [PMID: 34630391]

Giil, L.M.; Midttun, Ø.; Refsum, H.; Ulvik, A.; Advani, R.; Smith, A.D.; Ueland, P.M. Kynurenine pathway metabolites in Alzheimer’s Disease. J. Alzheimers Dis., 2017, 60(2), 495-504.
[http://dx.doi.org/10.3233/JAD-170485] [PMID: 28869479]

Gulaj, E.; Pawlak, K.; Bien, B.; Pawlak, D. Kynurenine and its metabolites in Alzheimer’s disease patients. Adv. Med. Sci., 2010, 55(2), 204-211.
[http://dx.doi.org/10.2478/v10039-010-0023-6] [PMID: 20639188]

Widner, B.; Leblhuber, F.; Walli, J.; Tilz, G.P.; Demel, U.; Fuchs, D. Tryptophan degradation and immune activation in Alzheimer’s disease. J. Neural Transm. (Vienna), 2000, 107(3), 343-353.
[http://dx.doi.org/10.1007/s007020050029] [PMID: 10821443]

Chatterjee, P.; Goozee, K.; Lim, C.K.; James, I.; Shen, K.; Jacobs, K.R.; Sohrabi, H.R.; Shah, T.; Asih, P.R.; Dave, P.; ManYan, C.; Taddei, K.; Lovejoy, D.B.; Chung, R.; Guillemin, G.J.; Martins, R.N. Alterations in serum kynurenine pathway metabolites in individuals with high neocortical amyloid-β load: A pilot study. Sci. Rep., 2018, 8(1), 8008.
[http://dx.doi.org/10.1038/s41598-018-25968-7] [PMID: 29789640]

Sorgdrager, F.J.H.; Vermeiren, Y.; Faassen, M.; Ley, C.; Nollen, E.A.A.; Kema, I.P.; De Deyn, P.P. Age‐ and disease‐specific changes of the kynurenine pathway in Parkinson’s and Alzheimer’s disease. J. Neurochem., 2019, 151(5), 656-668.
[http://dx.doi.org/10.1111/jnc.14843] [PMID: 31376341]

Morrens, M.; De Picker, L.; Kampen, J.K.; Coppens, V. Blood-based kynurenine pathway alterations in schizophrenia spectrum disorders: A meta-analysis. Schizophr. Res., 2020, 223, 43-52.
[http://dx.doi.org/10.1016/j.schres.2020.09.007] [PMID: 32981827]

Kouli, A.; Torsney, K.M.; Kuan, W.L. Parkinson’s Disease: Etiology, Neuropathology, and Pathogenesis. In: Stoker TB, Greenland JC, editors. Parkinson’s Disease: Pathogenesis and Clinical Aspects. Brisbane (AU): Codon Publications; , 2018. Dec 21; Chapter 1. Available from: https://www.ncbi.nlm.nih.gov/books/NBK536722/
[http://dx.doi.org/10.15586/codonpublications.parkinsonsdisease.2018.ch1]

Samii, A.; Nutt, J.G.; Ransom, B.R. Parkinson’s disease. Lancet, 2004, 363(9423), 1783-1793.
[http://dx.doi.org/10.1016/S0140-6736(04)16305-8] [PMID: 15172778]

Ogawa, T.; Matson, W.R.; Beal, M.F.; Myers, R.H.; Bird, E.D.; Milbury, P.; Saso, S. Kynurenine pathway abnormalities in Parkinson’s disease. Neurology, 1992, 42(9), 1702-1706.
[http://dx.doi.org/10.1212/WNL.42.9.1702] [PMID: 1513457]

Heilman, P.L.; Wang, E.W.; Lewis, M.M.; Krzyzanowski, S.; Capan, C.D.; Burmeister, A.R.; Du, G.; Escobar Galvis, M.L.; Brundin, P.; Huang, X.; Brundin, L. Tryptophan metabolites are associated with symptoms and nigral pathology in Parkinson’s Disease. Mov. Disord., 2020, 35(11), 2028-2037.
[http://dx.doi.org/10.1002/mds.28202] [PMID: 32710594]

Chang, K.H.; Cheng, M.L.; Tang, H.Y.; Huang, C.Y.; Wu, Y.R.; Chen, C.M. Alternations of metabolic profile and kynurenine metabolism in the plasma of Parkinson’s Disease. Mol. Neurobiol., 2018, 55(8), 6319-6328.
[http://dx.doi.org/10.1007/s12035-017-0845-3] [PMID: 29294246]

Oxenkrug, G.; van der Hart, M.; Roeser, J.; Summergrad, P. Peripheral Tryptophan-Kynurenine metabolism associated with metabolic syndrome is different in Parkinson’s and Alzheimer’s diseases. Endocrinol. Diabetes Metab. J., 2017, 1(4)
[PMID: 29292800]

Widner, B.; Leblhuber, F.; Fuchs, D. Increased neopterin production and tryptophan degradation in advanced Parkinson’s disease. J. Neural Transm. (Vienna), 2002, 109(2), 181-189.
[http://dx.doi.org/10.1007/s007020200014] [PMID: 12075858]

Bai, J.; Zheng, Y.; Yu, Y. Urinary kynurenine as a biomarker for Parkinson’s disease. Neurol. Sci., 2021, 42(2), 697-703.
[http://dx.doi.org/10.1007/s10072-020-04589-x] [PMID: 32661882]

Hartai, Z.; Klivenyi, P.; Janaky, T.; Penke, B.; Dux, L.; Vecsei, L. Kynurenine metabolism in plasma and in red blood cells in Parkinson’s disease. J. Neurol. Sci., 2005, 239(1), 31-35.
[http://dx.doi.org/10.1016/j.jns.2005.07.006] [PMID: 16099471]

Luan, H.; Liu, L.F.; Meng, N.; Tang, Z.; Chua, K.K.; Chen, L.L.; Song, J.X.; Mok, V.C.T.; Xie, L.X.; Li, M.; Cai, Z. LC-MS-based urinary metabolite signatures in idiopathic Parkinson’s disease. J. Proteome Res., 2015, 14(1), 467-478.
[http://dx.doi.org/10.1021/pr500807t] [PMID: 25271123]

Tohgi, H.; Abe, T.; Takahashi, S.; Kimura, M.; Takahashi, J.; Kikuchi, T. Concentrations of serotonin and its related substances in the cerebrospinal fluid in patients with Alzheimer type dementia. Neurosci. Lett., 1992, 141(1), 9-12.
[http://dx.doi.org/10.1016/0304-3940(92)90322-X] [PMID: 1508406]

Tohgi, H.; Abe, T.; Takahashi, S.; Takahashi, J.; Hamato, H. Concentrations of serotonin and its related substances in the cerebrospinal fluid of Parkinsonian patients and their relations to the severity of symptoms. Neurosci. Lett., 1993, 150(1), 71-74.
[http://dx.doi.org/10.1016/0304-3940(93)90111-W] [PMID: 7682308]

Zhang, S.; Collier, M.E.W.; Heyes, D.J.; Giorgini, F.; Scrutton, N.S. Advantages of brain penetrating inhibitors of kynurenine-3-monooxygenase for treatment of neurodegenerative diseases. Arch. Biochem. Biophys., 2021, 697, 108702.
[http://dx.doi.org/10.1016/j.abb.2020.108702] [PMID: 33275878]

Ghosh, R.; Tabrizi, S.J. Huntington disease. Handb. Clin. Neurol., 2018, 147, 255-278.
[http://dx.doi.org/10.1016/B978-0-444-63233-3.00017-8] [PMID: 29325616]

Giorgini, F.; Guidetti, P.; Nguyen, Q.; Bennett, S.C.; Muchowski, P.J. A genomic screen in yeast implicates kynurenine 3-monooxygenase as a therapeutic target for Huntington disease. Nat. Genet., 2005, 37(5), 526-531.
[http://dx.doi.org/10.1038/ng1542] [PMID: 15806102]

Breda, C.; Sathyasaikumar, K.V.; Sograte Idrissi, S.; Notarangelo, F.M.; Estranero, J.G.; Moore, G.G.L.; Green, E.W.; Kyriacou, C.P.; Schwarcz, R.; Giorgini, F. Tryptophan-2,3-dioxygenase (TDO) inhibition ameliorates neurodegeneration by modulation of kynurenine pathway metabolites. Proc. Natl. Acad. Sci. USA, 2016, 113(19), 5435-5440.
[http://dx.doi.org/10.1073/pnas.1604453113] [PMID: 27114543]

Zwilling, D.; Huang, S.Y.; Sathyasaikumar, K.V.; Notarangelo, F.M.; Guidetti, P.; Wu, H.Q.; Lee, J.; Truong, J.; Andrews-Zwilling, Y.; Hsieh, E.W.; Louie, J.Y.; Wu, T.; Scearce-Levie, K.; Patrick, C.; Adame, A.; Giorgini, F.; Moussaoui, S.; Laue, G.; Rassoulpour, A.; Flik, G.; Huang, Y.; Muchowski, J.M.; Masliah, E.; Schwarcz, R.; Muchowski, P.J. Kynurenine 3-monooxygenase inhibition in blood ameliorates neurodegeneration. Cell, 2011, 145(6), 863-874.
[http://dx.doi.org/10.1016/j.cell.2011.05.020] [PMID: 21640374]

Beconi, M.G.; Yates, D.; Lyons, K.; Matthews, K.; Clifton, S.; Mead, T.; Prime, M.; Winkler, D.; O’Connell, C.; Walter, D.; Toledo-Sherman, L.; Munoz-Sanjuan, I.; Dominguez, C. Metabolism and pharmacokinetics of JM6 in mice: JM6 is not a prodrug for Ro-61-8048. Drug Metab. Dispos., 2012, 40(12), 2297-2306.
[http://dx.doi.org/10.1124/dmd.112.046532] [PMID: 22942319]

Röver, S.; Cesura, A.M.; Huguenin, P.; Kettler, R.; Szente, A. Synthesis and biochemical evaluation of N-(4-phenylthiazol-2-yl)benzenesulfonamides as high-affinity inhibitors of kynurenine 3-hydroxylase. J. Med. Chem., 1997, 40(26), 4378-4385.
[http://dx.doi.org/10.1021/jm970467t] [PMID: 9435907]

Sodhi, R.K.; Bansal, Y.; Singh, R.; Saroj, P.; Bhandari, R.; Kumar, B.; Kuhad, A. IDO-1 inhibition protects against neuroinflammation, oxidative stress and mitochondrial dysfunction in 6-OHDA induced murine model of Parkinson’s disease. Neurotoxicology, 2021, 84, 184-197.
[http://dx.doi.org/10.1016/j.neuro.2021.03.009] [PMID: 33774066]

Marim, F.M.; Teixeira, D.C.; Queiroz-Junior, C.M.; Valiate, B.V.S.; Alves-Filho, J.C.; Cunha, T.M.; Dantzer, R.; Teixeira, M.M.; Teixeira, A.L.; Costa, V.V. Inhibition of tryptophan catabolism is associated with neuroprotection during zika virus infection. Front. Immunol., 2021, 12, 702048.
[http://dx.doi.org/10.3389/fimmu.2021.702048] [PMID: 34335614]

Guo, Y.; Liu, Y.; Wu, W.; Ling, D.; Zhang, Q.; Zhao, P.; Hu, X. Indoleamine 2,3-dioxygenase (Ido) inhibitors and their nanomedicines for cancer immunotherapy. Biomaterials, 2021, 276, 121018.
[http://dx.doi.org/10.1016/j.biomaterials.2021.121018] [PMID: 34284200]

Modoux, M.; Rolhion, N.; Mani, S.; Sokol, H. Tryptophan metabolism as a pharmacological target. Trends Pharmacol. Sci., 2021, 42(1), 60-73.
[http://dx.doi.org/10.1016/j.tips.2020.11.006] [PMID: 33256987]

Ojo, E.S.; Tischkau, S.A. The role of AhR in the hallmarks of brain aging: Friend and foe. Cells, 2021, 10(10), 2729.
[http://dx.doi.org/10.3390/cells10102729] [PMID: 34685709]

Sun, M.; Ma, N.; He, T.; Johnston, L.J.; Ma, X. Tryptophan (Trp) modulates gut homeostasis via aryl hydrocarbon receptor (AhR). Crit. Rev. Food Sci. Nutr., 2020, 60(10), 1760-1768.
[http://dx.doi.org/10.1080/10408398.2019.1598334] [PMID: 30924357]

Doifode, T.; Giridharan, V.V.; Generoso, J.S.; Bhatti, G.; Collodel, A.; Schulz, P.E.; Forlenza, O.V.; Barichello, T. The impact of the microbiota-gut-brain axis on Alzheimer’s disease pathophysiology. Pharmacol. Res., 2021, 164, 105314.
[http://dx.doi.org/10.1016/j.phrs.2020.105314] [PMID: 33246175]

Agus, A.; Planchais, J.; Sokol, H. Gut microbiota regulation of tryptophan metabolism in health and disease. Cell Host Microbe, 2018, 23(6), 716-724.
[http://dx.doi.org/10.1016/j.chom.2018.05.003] [PMID: 29902437]

Santoro, A.; Ostan, R.; Candela, M.; Biagi, E.; Brigidi, P.; Capri, M.; Franceschi, C. Gut microbiota changes in the extreme decades of human life: A focus on centenarians. Cell. Mol. Life Sci., 2018, 75(1), 129-148.
[http://dx.doi.org/10.1007/s00018-017-2674-y] [PMID: 29032502]

Rajilić-Stojanović M.; de Vos, W.M. The first 1000 cultured species of the human gastrointestinal microbiota. FEMS Microbiol. Rev., 2014, 38(5), 996-1047.
[http://dx.doi.org/10.1111/1574-6976.12075] [PMID: 24861948]

Lozupone, C.A.; Stombaugh, J.I.; Gordon, J.I.; Jansson, J.K.; Knight, R. Diversity, stability and resilience of the human gut microbiota. Nature, 2012, 489(7415), 220-230.
[http://dx.doi.org/10.1038/nature11550] [PMID: 22972295]

Eckburg, P.B.; Bik, E.M.; Bernstein, C.N.; Purdom, E.; Dethlefsen, L.; Sargent, M.; Gill, S.R.; Nelson, K.E.; Relman, D.A. Diversity of the human intestinal microbial flora. Science, 2005, 308(5728), 1635-1638.
[http://dx.doi.org/10.1126/science.1110591] [PMID: 15831718]

Biagi, E.; Franceschi, C.; Rampelli, S.; Severgnini, M.; Ostan, R.; Turroni, S.; Consolandi, C.; Quercia, S.; Scurti, M.; Monti, D.; Capri, M.; Brigidi, P.; Candela, M. Gut microbiota and extreme longevity. Curr. Biol., 2016, 26(11), 1480-1485.
[http://dx.doi.org/10.1016/j.cub.2016.04.016] [PMID: 27185560]

Martins, L.B.; Malheiros Silveira, A.L.; Teixeira, A.L. The link between nutrition and Alzheimer’s disease: From prevention to treatment. Neurodegener. Dis. Manag., 2021, 11(2), 155-166.
[http://dx.doi.org/10.2217/nmt-2020-0023] [PMID: 33550870]

Liddle, RA Parkinson's disease from the gut. Brain Res., 2018, 1693(Pt B), 201-6.

Pluta, R. Ułamek-Kozioł M.; Januszewski, S.; Czuczwar, S.J. Gut microbiota and pro/prebiotics in Alzheimer’s disease. Aging (Albany NY), 2020, 12(6), 5539-5550.
[http://dx.doi.org/10.18632/aging.102930] [PMID: 32191919]

Leblhuber, F.; Steiner, K.; Schuetz, B.; Fuchs, D.; Gostner, J.M. Probiotic supplementation in patients with Alzheimer’s Dementia-an explorative intervention study. Curr. Alzheimer Res., 2018, 15(12), 1106-1113.
[http://dx.doi.org/10.2174/1389200219666180813144834] [PMID: 30101706]

Ulvik, A.; Theofylaktopoulou, D.; Midttun, Ø.; Nygård, O.; Eussen, S.J.P.M.; Ueland, P.M. Substrate product ratios of enzymes in the kynurenine pathway measured in plasma as indicators of functional vitamin B-6 status. Am. J. Clin. Nutr., 2013, 98(4), 934-940.
[http://dx.doi.org/10.3945/ajcn.113.064998] [PMID: 24004893]

Midttun, Ø.; Ulvik, A.; Ringdal Pedersen, E.; Ebbing, M.; Bleie, Ø.; Schartum-Hansen, H.; Nilsen, R.M.; Nygård, O.; Ueland, P.M. Low plasma vitamin B-6 status affects metabolism through the kynurenine pathway in cardiovascular patients with systemic inflammation. J. Nutr., 2011, 141(4), 611-617.
[http://dx.doi.org/10.3945/jn.110.133082] [PMID: 21310866]

Hughes, C.; Ward, M.; Tracey, F.; Hoey, L.; Molloy, A.; Pentieva, K.; McNulty, H. B-Vitamin intake and biomarker status in relation to cognitive decline in healthy older adults in a 4-year follow-up study. Nutrients, 2017, 9(1), 53.
[http://dx.doi.org/10.3390/nu9010053] [PMID: 28075382]

Corrada, M.M.; Kawas, C.H.; Hallfrisch, J.; Muller, D.; Brookmeyer, R. Reduced risk of Alzheimer’s disease with high folate intake: The baltimore longitudinal study of aging. Alzheimers Dement., 2005, 1(1), 11-18.
[http://dx.doi.org/10.1016/j.jalz.2005.06.001] [PMID: 19595811]

Smith, A.D.; Refsum, H.; Bottiglieri, T.; Fenech, M.; Hooshmand, B.; McCaddon, A.; Miller, J.W.; Rosenberg, I.H.; Obeid, R. Homocysteine and dementia: An international consensus statement1. J. Alzheimers Dis., 2018, 62(2), 561-570.
[http://dx.doi.org/10.3233/JAD-171042] [PMID: 29480200]

Tanaka, M.; Bohár, Z.; Vécsei, L. Are kynurenines accomplices or principal villains in dementia? Maintenance of kynurenine metabolism. Molecules, 2020, 25(3), 564.
[http://dx.doi.org/10.3390/molecules25030564] [PMID: 32012948]

Flint Beal, M.; Matson, W.R.; Storey, E.; Milbury, P.; Ryan, E.A.; Ogawa, T.; Bird, E.D. Kynurenic acid concentrations are reduced in Huntington’s disease cerebral cortex. J. Neurol. Sci., 1992, 108(1), 80-87.
[http://dx.doi.org/10.1016/0022-510X(92)90191-M] [PMID: 1385624]

Heyes, M.P.; Saito, K.; Crowley, J.S.; Davis, L.E.; Demitrack, M.A.; Der, M.; Dilling, L.A.; Elia, J.; Kruesi, M.J.P.; Lackner, A.; Larsen, S.A.; Lee, K.; Leonard, H.L.; Markey, S.P.; Martin, A.; Milstein, S.; Mouradian, M.M.; Pranzatelli, M.R.; Quearry, B.J.; Salazar, A.; Smith, M.; Strauss, S.E.; Sunderland, T.; Swedo, S.W.; Tourtellotte, W.W. Quinolinic acid and kynurenine pathway metabolism in inflammatory and non-inflammatory neurological disease. Brain, 1992, 115(5), 1249-1273.
[http://dx.doi.org/10.1093/brain/115.5.1249] [PMID: 1422788]

Pearson, S.J.; Reynolds, G.P. Increased brain concentrations of a neurotoxin, 3-hydroxykynurenine, in Huntington’s disease. Neurosci. Lett., 1992, 144(1-2), 199-201.
[http://dx.doi.org/10.1016/0304-3940(92)90749-W] [PMID: 1436703]

Baran, H.; Jellinger, K.; Deecke, L. Kynurenine metabolism in Alzheimer’s disease. J. Neural Transm. (Vienna), 1999, 106(2), 165-181.
[http://dx.doi.org/10.1007/s007020050149] [PMID: 10226937]

Schwarz, M.J.; Guillemin, G.J.; Teipel, S.J.; Buerger, K.; Hampel, H. Increased 3-Hydroxykynurenine serum concentrations differentiate Alzheimer’s disease patients from controls. Eur. Arch. Psychiatry Clin. Neurosci., 2013, 263(4), 345-352.
[http://dx.doi.org/10.1007/s00406-012-0384-x] [PMID: 23192697]

Muguruma, Y.; Tsutsui, H.; Noda, T.; Akatsu, H.; Inoue, K. Widely targeted metabolomics of Alzheimer’s disease postmortem cerebrospinal fluid based on 9-fluorenylmethyl chloroformate derivatized ultra-high performance liquid chromatography tandem mass spectrometry. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2018, 1091, 53-66.
[http://dx.doi.org/10.1016/j.jchromb.2018.05.031] [PMID: 29852382]

Whiley, L.; Chappell, K.E.; D’Hondt, E.; Lewis, M.R.; Jiménez, B.; Snowden, S.G.; Soininen, H. Kłoszewska, I.; Mecocci, P.; Tsolaki, M.; Vellas, B.; Swann, J.R.; Hye, A.; Lovestone, S.; Legido-Quigley, C.; Holmes, E. Metabolic phenotyping reveals a reduction in the bioavailability of serotonin and kynurenine pathway metabolites in both the urine and serum of individuals living with Alzheimer’s disease. Alzheimers Res. Ther., 2021, 13(1), 20.
[http://dx.doi.org/10.1186/s13195-020-00741-z] [PMID: 33422142]

Willette, A.A.; Pappas, C.; Hoth, N.; Wang, Q.; Klinedinst, B.; Willette, S.A.; Larsen, B.; Pollpeter, A.; Li, T.; Le, S.; Collazo-Martinez, A.D.; Mochel, J.P.; Allenspach, K.; Dantzer, R. Inflammation, negative affect, and amyloid burden in Alzheimer’s disease: Insights from the kynurenine pathway. Brain Behav. Immun., 2021, 95, 216-225.
[http://dx.doi.org/10.1016/j.bbi.2021.03.019] [PMID: 33775832]

LeWitt, P.A.; Li, J.; Lu, M.; Beach, T.G.; Adler, C.H.; Guo, L. 3-hydroxykynurenine and other Parkinson’s disease biomarkers discovered by metabolomic analysis. Mov. Disord., 2013, 28(12), 1653-1660.
[http://dx.doi.org/10.1002/mds.25555] [PMID: 23873789]

Iwaoka, K.; Otsuka, C.; Maeda, T.; Yamahara, K.; Kato, K.; Takahashi, K.; Takahashi, K.; Terayama, Y. Impaired metabolism of kynurenine and its metabolites in CSF of parkinson’s disease. Neurosci. Lett., 2020, 714, 134576.
[http://dx.doi.org/10.1016/j.neulet.2019.134576] [PMID: 31654722]