The Influence of Kynurenine Metabolites on Neurodegenerative Pathologies

被引:23
作者
Pathak, Suhrud [1 ]
Nadar, Rishi [1 ]
Kim, Shannon [1 ]
Liu, Keyi [1 ]
Govindarajulu, Manoj [2 ]
Cook, Preston [1 ]
Alexander, Courtney S. Watts [3 ]
Dhanasekaran, Muralikrishnan [1 ]
Moore, Timothy [1 ]
机构
[1] Auburn Univ, Harrison Coll Pharm, Dept Drug Discovery & Dev, Auburn, AL 36849 USA
[2] Walter Reed Army Inst Res, Ctr Mil Psychiat & Neurosci, Blast Induced Neurotrauma Branch, Silver Spring, MD 20910 USA
[3] Auburn Univ, Harrison Coll Pharm, Dept Pharm Practice, Auburn, AL 36849 USA
关键词
kynurenine pathway; neurological pathologies; inflammation; tryptophan; Alzheimer's disease; Parkinson's disease; THERAPEUTIC TARGET; ALZHEIMERS-DISEASE; TRYPTOPHAN DEGRADATION; NEOPTERIN PRODUCTION; CEREBROSPINAL-FLUID; QUINOLINIC ACID; PATHWAY ENZYMES; RAT-BRAIN; EXPRESSION; INFLAMMATION;
D O I
10.3390/ijms25020853
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
As the kynurenine pathway's links to inflammation, the immune system, and neurological disorders became more apparent, it attracted more and more attention. It is the main pathway through which the liver breaks down Tryptophan and the initial step in the creation of nicotinamide adenine dinucleotide (NAD+) in mammals. Immune system activation and the buildup of potentially neurotoxic substances can result from the dysregulation or overactivation of this pathway. Therefore, it is not shocking that kynurenines have been linked to neurological conditions (Depression, Parkinson's, Alzheimer's, Huntington's Disease, Schizophrenia, and cognitive deficits) in relation to inflammation. Nevertheless, preclinical research has demonstrated that kynurenines are essential components of the behavioral analogs of depression and schizophrenia-like cognitive deficits in addition to mediators associated with neurological pathologies due to their neuromodulatory qualities. Neurodegenerative diseases have been extensively associated with neuroactive metabolites of the kynurenine pathway (KP) of tryptophan breakdown. In addition to being a necessary amino acid for protein synthesis, Tryptophan is also transformed into the important neurotransmitters tryptamine and serotonin in higher eukaryotes. In this article, a summary of the KP, its function in neurodegeneration, and the approaches being used currently to target the route therapeutically are discussed.
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页数:15
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共 91 条
  • [61] Cognitive deficit induced by acute tryptophan depletion in patients with Alzheimer's disease
    Porter, RJ
    Lunn, BS
    Walker, LLM
    Gray, JM
    Ballard, CG
    O'Brien, JT
    [J]. AMERICAN JOURNAL OF PSYCHIATRY, 2000, 157 (04) : 638 - 640
  • [62] Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia
    Rascovsky, Katya
    Hodges, John R.
    Knopman, David
    Mendez, Mario F.
    Kramer, Joel H.
    Neuhaus, John
    van Swieten, John C.
    Seelaar, Harro
    Dopper, Elise G. P.
    Onyike, Chiadi U.
    Hillis, Argye E.
    Josephs, Keith A.
    Boeve, Bradley F.
    Kertesz, Andrew
    Seeley, William W.
    Rankin, Katherine P.
    Johnson, Julene K.
    Gorno-Tempini, Maria-Luisa
    Rosen, Howard
    Prioleau-Latham, Caroline E.
    Lee, Albert
    Kipps, Christopher M.
    Lillo, Patricia
    Piguet, Olivier
    Rohrer, Jonathan D.
    Rossor, Martin N.
    Warren, Jason D.
    Fox, Nick C.
    Galasko, Douglas
    Salmon, David P.
    Black, Sandra E.
    Mesulam, Marsel
    Weintraub, Sandra
    Dickerson, Brad C.
    Diehl-Schmid, Janine
    Pasquier, Florence
    Deramecourt, Vincent
    Lebert, Florence
    Pijnenburg, Yolande
    Chow, Tiffany W.
    Manes, Facundo
    Grafman, Jordan
    Cappa, Stefano F.
    Freedman, Morris
    Grossman, Murray
    Miller, Bruce L.
    [J]. BRAIN, 2011, 134 : 2456 - 2477
  • [63] Richard DM, 2009, INT J TRYPTOPHAN RES, V2, P45
  • [64] Kynurenine pathway metabolites in cerebrospinal fluid and blood as potential biomarkers in Huntington's disease
    Rodrigues, Filipe B.
    Byrne, Lauren M.
    Lowe, Alexander J.
    Tortelli, Rosanna
    Heins, Mariette
    Flik, Gunnar
    Johnson, Eileanoir B.
    De Vita, Enrico
    Scahill, Rachael I.
    Giorgini, Flaviano
    Wild, Edward J.
    [J]. JOURNAL OF NEUROCHEMISTRY, 2021, 158 (02) : 539 - 553
  • [65] The kynurenine pathway: a finger in every pie
    Savitz, Jonathan
    [J]. MOLECULAR PSYCHIATRY, 2020, 25 (01) : 131 - 147
  • [66] Kynurenine Metabolism and Alzheimer's Disease: The Potential Targets and Approaches
    Sharma, Vivek Kumar
    Singh, Thakur Gurjeet
    Prabhakar, Nirbhay Kumar
    Mannan, Ashi
    [J]. NEUROCHEMICAL RESEARCH, 2022, 47 (06) : 1459 - 1476
  • [67] Inflammatory markers in Alzheimer's disease and mild cognitive impairment: a meta-analysis and systematic review of 170 studies
    Shen, Xue-Ning
    Niu, Li-Dong
    Wang, Yan-Jiang
    Cao, Xi-Peng
    Liu, Qiang
    Tan, Lan
    Zhang, Can
    Yu, Jin-Tai
    [J]. JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, 2019, 90 (05) : 590 - 598
  • [68] Kynurenines, Neuropsychiatric Symptoms, and Cognitive Prognosis in Patients with Mild Dementia
    Soivang, Stein-Erik Hafstad
    Nordrehaug, Jan Erik
    Aarsland, Dag
    Lange, Johannes
    Ueland, Per Magne
    McCann, Adrian
    Midttun, Oivind
    Tell, Grethe S.
    Giil, Lasse Melvaer
    [J]. INTERNATIONAL JOURNAL OF TRYPTOPHAN RESEARCH, 2019, 12
  • [69] Kynurenine Pathway Metabolites in the Blood and Cerebrospinal Fluid Are Associated with Human Aging
    Solvang, Stein-Erik H.
    Hodge, Allison
    Watne, Leiv Otto
    Cabral-Marques, Otavio
    Nordrehaug, Jan Erik
    Giles, Graham G.
    Dugue, Pierre-Antoine
    Nygard, Ottar
    Ueland, Per Magne
    McCann, Adrian
    Idland, Ane-Victoria
    Midttun, Oivind
    Ulvik, Arve
    Halaas, Nathalie B.
    Tell, Grethe S.
    Giil, Lasse M.
    [J]. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY, 2022, 2022
  • [70] Age- and disease-specific changes of the kynurenine pathway in Parkinson's and Alzheimer's disease
    Sorgdrager, Freek J. H.
    Vermeiren, Yannick
    Van Faassen, Arti N.
    van der Ley, Claude
    Nollen, Ellen A. A.
    Kema, Ido P.
    De Deyn, Peter P.
    [J]. JOURNAL OF NEUROCHEMISTRY, 2019, 151 (05) : 656 - 668