Single Nucleotide Polymorphisms of Indoleamine 2,3-Dioxygenase Influenced the Age Onset of Parkinson’s Disease

Török, Nóra; Maszlag-Török, Rita; Molnár, Kriszta; Szolnoki, Zoltán; Somogyvári, Ferenc; Boda, Krisztina; Tanaka, Masaru; Klivényi, Péter; Vécsei, László

doi:10.20944/preprints202010.0172.v2

Cited by 5 publications

(4 citation statements)

References 42 publications

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“…Increased 3-HK levels in CSF and a lower KYNA/KYN ratio, increased QUIN levels, and higher QUIN/KYNA ratio were reported in plasma of PD patients [186,187]. In addition, it is reported that the single nuclear polymorphism variants of IDO1 influence the age onset of PD [188]. PD had strong effect sizes for shared deficits in complex I and IV in the peripheral blood, frontal cortex, cerebellum, and substantia nigra [173].…”

Section: Parkinson's Diseasementioning

confidence: 98%

Mitochondrial Impairment: A Common Motif in Neuropsychiatric Presentation? The Link to the Tryptophan-Kynurenine Metabolic System

Tanaka¹,

Szabó²,

Spekker³

et al. 2022

Preprint

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Nearly half a century has passed since the discovery of cytoplasmic inheritance of human chloramphenicol resistance. The inheritance was then revealed to take place maternally by mitochondrial DNA (mtDNA). Later, a number of mutations in mtDNA were identified as a cause of severe inheritable metabolic diseases with neurological manifestation, and the impairment of mitochondrial functions has been probed in the pathogenesis of a wide range of illnesses including neurodegenerative diseases. Recently growing number of preclinical studies has revealed that animal behaviors are influenced by the impairment of mitochondrial functions and possibly by the loss of mitochondrial stress resilience. Indeed, as high as 54% of patients with one of the most common primary mitochondrial diseases, mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome, present psychiatric symptoms including cognitive impairment, mood disorder, anxiety, and psychosis. Mitochondria are multifunctional organelles which produce cellular energy and play a major role in other cellular functions including homeostasis, cellular signaling, and gene expression, among other. Mitochondrial functions are observed to be compromised and to become less resilient under continuous stress. Meanwhile, stress and inflammation have been linked to the activation of the tryptophan (Trp)-kynurenine (KYN) metabolic system, which observably contributes to development of pathological conditions including neurological and psychiatric disorders. This narrative review discusses the functions of mitochondria and the Trp-KYN system, the interaction of the Trp-KYN system with mitochondria, and the current understanding of the involvement of mitochondria and the Trp-KYN system in preclinical and clinical studies of major neurological and psychiatric diseases.

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Section: Parkinson's Diseasementioning

confidence: 98%

Mitochondrial Impairment: A Common Motif in Neuropsychiatric Presentation? The Link to the Tryptophan-Kynurenine Metabolic System

Tanaka¹,

Szabó²,

Spekker³

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Increased 3-HK levels in CSF and a lower KYNA/KYN ratio, increased QUIN levels, and higher QUIN/KYNA ratio were reported in plasma of PD patients [ 205 , 206 ]. In addition, it is reported that the single nuclear polymorphism variants of IDO1 influence the age onset of PD [ 207 ]. PD had strong effect sizes for shared deficits in complex I and IV in the peripheral blood, frontal cortex, cerebellum, and substantia nigra [ 192 ] ( Table 2 ).…”

Section: Diseases Linked To Mitochondrial Dysfunctionmentioning

confidence: 99%

Mitochondrial Impairment: A Common Motif in Neuropsychiatric Presentation? The Link to the Tryptophan–Kynurenine Metabolic System

Tanaka

Szabó

Spekker

et al. 2022

Cells

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119

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Nearly half a century has passed since the discovery of cytoplasmic inheritance of human chloramphenicol resistance. The inheritance was then revealed to take place maternally by mitochondrial DNA (mtDNA). Later, a number of mutations in mtDNA were identified as a cause of severe inheritable metabolic diseases with neurological manifestation, and the impairment of mitochondrial functions has been probed in the pathogenesis of a wide range of illnesses including neurodegenerative diseases. Recently, a growing number of preclinical studies have revealed that animal behaviors are influenced by the impairment of mitochondrial functions and possibly by the loss of mitochondrial stress resilience. Indeed, as high as 54% of patients with one of the most common primary mitochondrial diseases, mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome, present psychiatric symptoms including cognitive impairment, mood disorder, anxiety, and psychosis. Mitochondria are multifunctional organelles which produce cellular energy and play a major role in other cellular functions including homeostasis, cellular signaling, and gene expression, among others. Mitochondrial functions are observed to be compromised and to become less resilient under continuous stress. Meanwhile, stress and inflammation have been linked to the activation of the tryptophan (Trp)–kynurenine (KYN) metabolic system, which observably contributes to the development of pathological conditions including neurological and psychiatric disorders. This review discusses the functions of mitochondria and the Trp-KYN system, the interaction of the Trp-KYN system with mitochondria, and the current understanding of the involvement of mitochondria and the Trp-KYN system in preclinical and clinical studies of major neurological and psychiatric diseases.

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“…Van Gool et al also found a connection between IFN-α immunotherapy and psychiatric side effect [90]. IFN-α induces IDO, which converts TRP to KYN leading to a shortage of 5-HT, which may result in depression [38,91] (Table 1). IDO induction, a switch toward the TRP-KYN metabolic pathway and the disruption of the equilibrium between neurotoxic and neuroprotective actions all confirm the significance of KYN system activation in depression [92].…”

Section: Kynurenine Aminotransferasesmentioning

confidence: 99%

Immune Influencers in Action: Metabolites and Enzymes of the Tryptophan-Kynurenine Metabolic Pathway

et al. 2021

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The tryptophan (TRP)-kynurenine (KYN) metabolic pathway is a main player of TRP metabolism through which more than 95% of TRP is catabolized. The pathway is activated by acute and chronic immune responses leading to a wide range of illnesses including cancer, immune diseases, neurodegenerative diseases and psychiatric disorders. The presence of positive feedback loops facilitates amplifying the immune responses vice versa. The TRP-KYN pathway synthesizes multifarious metabolites including oxidants, antioxidants, neurotoxins, neuroprotectants and immunomodulators. The immunomodulators are known to facilitate the immune system towards a tolerogenic state, resulting in chronic low-grade inflammation (LGI) that is commonly present in obesity, poor nutrition, exposer to chemicals or allergens, prodromal stage of various illnesses and chronic diseases. KYN, kynurenic acid, xanthurenic acid and cinnabarinic acid are aryl hydrocarbon receptor ligands that serve as immunomodulators. Furthermore, TRP-KYN pathway enzymes are known to be activated by the stress hormone cortisol and inflammatory cytokines, and genotypic variants were observed to contribute to inflammation and thus various diseases. The tryptophan 2,3-dioxygenase, the indoleamine 2,3-dioxygenases and the kynurenine-3-monooxygenase are main enzymes in the pathway. This review article discusses the TRP-KYN pathway with special emphasis on its interaction with the immune system and the tolerogenic shift towards chronic LGI and overviews the major symptoms, pro- and anti-inflammatory cytokines and toxic and protective KYNs to explore the linkage between chronic LGI, KYNs, and major psychiatric disorders, including depressive disorder, bipolar disorder, substance use disorder, post-traumatic stress disorder, schizophrenia and autism spectrum disorder.

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Single Nucleotide Polymorphisms of Indoleamine 2,3-Dioxygenase Influenced the Age Onset of Parkinson’s Disease

Cited by 5 publications

References 42 publications

Mitochondrial Impairment: A Common Motif in Neuropsychiatric Presentation? The Link to the Tryptophan-Kynurenine Metabolic System

Mitochondrial Impairment: A Common Motif in Neuropsychiatric Presentation? The Link to the Tryptophan-Kynurenine Metabolic System

Mitochondrial Impairment: A Common Motif in Neuropsychiatric Presentation? The Link to the Tryptophan–Kynurenine Metabolic System

Immune Influencers in Action: Metabolites and Enzymes of the Tryptophan-Kynurenine Metabolic Pathway

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