Exploring the roles of tryptophan metabolism in MS beyond neuroinflammation and neurodegeneration: A paradigm shift to neuropsychiatric symptoms

Tan, Lorraine S. Y.; Francis, Heather; Lim, Chai K.

doi:10.1016/j.bbih.2021.100201

Cited by 3 publications

(2 citation statements)

References 96 publications

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“…In line with our findings, decreased TRP levels in plasma obtained from pwMS have been previously reported [31,32]. Recent studies have shown that activation of the kynurenine pathway (KP), responsible for more than 95% of TRP degradation, plays a key role in MS pathogenesis by modulating cell-mediated immune responses and may be associated with disease progression [33,34]. Lim et al found decreased serum TRP concentrations and a significantly higher kynurenine/tryptophan ratio in pwMS compared to HCs, and this was more pronounced in those with progressive disease types, suggesting that abnormalities in the KP may be associated with the conversion from early-mild stage to progressive MS forms, which is consistent with our findings [35].…”

Section: Discussionsupporting

confidence: 90%

Serum amino acid profiling in differentiating clinical outcomes of multiple sclerosis

Rzepiński¹,

Kośliński

Kowalewski³

et al. 2023

Neurol Neurochir Pol.

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Aim of the study. Amino acid metabolism is crucial for regulating immune responses and can be monitored in blood serum samples. This study aimed to analyse serum amino acid profiles in people with multiple sclerosis (pwMS), taking into account differences depending on the disease outcomes.Clinical rationale for the study. Serum amino acid profiling is a promising, reproducible and minimally invasive technology, available at different stages of the disease, enabling the search for a specific biomarker to differentiate MS clinical outcomes. Material and methods.The serum concentrations of 29 amino acids were determined using high-performance liquid chromatography mass spectrometry. Results.A total of 121 pwMS (41 relapsing-remitting MS-RRMS; 55 secondary progressive MS -SPMS; and 25 primary progressive MS-RRMS) with a median Expanded Disability Status Scale (EDSS) score of 6 and 53 healthy controls (HCs) were included. We found significantly higher serum total amino acids concentrations in pwMS compared to HCs. Serum concentrations of arginine, 1-methyl-L-histidine and proline were higher in pwMS, while circulating citrulline, α-aminobutyric acid and tryptophan were lower in pwMS. We observed significant differences in serum total amino acids concentrations depending on MS type, with the highest level in the PPMS group and the lowest in the RRMS group. We found significantly higher serum levels of beta-aminoisobutyric acid in PPMS patients compared to those with RRMS and SPMS, and significantly higher serum levels of aspartic acid in PPMS patients compared to RRMS patients. From visual inspection, no trend was observed in total amino acids concentration with respect to the EDSS score. When analysing serum total amino acids concentration in pwMS with EDSS ≤ 5 compared to those with EDSS > 5, no significant differences were found.Conclusions and clinical implications. Amino acid metabolism is altered in pwMS and depends on the clinical type of the disease. Further studies are needed to determine whether serum metabolomic profiling of amino acids may have an application in the search for clinical phenotype-specific MS biomarkers.

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Section: Discussionsupporting

confidence: 90%

Serum amino acid profiling in differentiating clinical outcomes of multiple sclerosis

Rzepiński¹,

Kośliński

Kowalewski³

et al. 2023

Neurol Neurochir Pol.

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“…Our result reflects a broader implication and link with immune regulators such as the aryl hydrocarbon receptor and interactions with the kynurenine pathway in modulating MS progression, relevant to our MS cohort ( Bessede et al., 2014 ; Yan et al., 2010 ). It would be of interest to examine how the kynurenine pathway fits into our current hypothesis considering its role in both mood and immune regulation in MS ( Tan et al., 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Innate immunity impacts social-cognitive functioning in people with multiple sclerosis and healthy individuals: Implications for IL-1ra and urinary immune markers

Turner

Padgett

McDonald

et al. 2021

Brain, Behavior, & Immunity - Health

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Social-cognitive difficulties can negatively impact interpersonal communication, shared social experience, and meaningful relationships. This pilot investigation examined the relationship between social-cognitive functioning and inflammatory markers in people with multiple sclerosis (MS) and demographically-matched healthy individuals. Additionally, we compared the immune marker profile in serum and urine-matched samples. Social cognitive functioning was objectively assessed using The Awareness of Social Inference Test – Short (TASIT-S) and subjectively assessed using self-reports of abilities in emotion recognition, emotional empathy, and cognitive theory of mind. In people with MS and healthy individuals, there were moderate-to-large negative relationships between pro-inflammatory biomarkers (serum IL-1β, IL-17, TNF-α, IP-10, MIP-1α, and urine IP-10, MIP-1β) of the innate immune system and social-cognitive functioning. In MS, a higher serum concentration of the anti-inflammatory marker IL-1ra was associated with better social-cognitive functioning (i.e., self-reported emotional empathy and TASIT-S sarcasm detection performance). However, there were mixed findings for anti-inflammatory serum markers IL-4 and IL-10. Overall, our findings indicate a relationship between pro-inflammatory cytokines and social-cognitive abilities. Future studies may provide greater insight into biologically-derived inflammatory processes, sickness behaviour, and their connection with social cognition.

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Kynurenines and Inflammation: A Remarkable Axis for Multiple Sclerosis Treatment

Carrillo-Mora,

Landa-Solís,

Valle-Garcia

et al. 2024

Pharmaceuticals

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Multiple sclerosis (MS) is a chronic inflammatory autoimmune neurological disease characterized by the recurrent appearance of demyelinating lesions and progressive disability. Currently, there are multiple disease-modifying treatments, however, there is a significant need to develop new therapeutic targets, especially for the progressive forms of the disease. This review article provides an overview of the most recent studies aimed at understanding the inflammatory processes that are activated in response to the accumulation of kynurenine pathway (KP) metabolites, which exacerbate an imbalance between immune system cells (e.g., Th1, Th2, and T reg) and promote the release of pro-inflammatory interleukins that modulate different mechanisms: membrane-receptors function; nuclear factors expression; and cellular signals. Together, these alterations trigger cell death mechanisms in brain cells and promote neuron loss and axon demyelination. This hypothesis could represent a remarkable approach for disease-modifying therapies for MS. Here, we also provide a perspective on the repositioning of some already approved drugs involved in other signaling pathways, which could represent new therapeutic strategies for MS treatment.

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Exploring the roles of tryptophan metabolism in MS beyond neuroinflammation and neurodegeneration: A paradigm shift to neuropsychiatric symptoms

Cited by 3 publications

References 96 publications

Serum amino acid profiling in differentiating clinical outcomes of multiple sclerosis

Serum amino acid profiling in differentiating clinical outcomes of multiple sclerosis

Innate immunity impacts social-cognitive functioning in people with multiple sclerosis and healthy individuals: Implications for IL-1ra and urinary immune markers

Kynurenines and Inflammation: A Remarkable Axis for Multiple Sclerosis Treatment

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