Searching for Peripheral Biomarkers in Neurodegenerative Diseases: The Tryptophan-Kynurenine Metabolic Pathway

Török, Nóra; Tanaka, Masaru; Vécsei, László

doi:10.3390/ijms21249338

Cited by 104 publications

(89 citation statements)

References 151 publications

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“…In recent years, studies of AD, PD and ALS have revealed pathological pathways present in other tissues. Due to some similarities in the peripheral effects in various neurodegenerative disorders, it is worth considering biomarkers which can be used for each of these diseases [ 153 ]. Nevertheless, specific diseases, such as HD, are also characterized by some specific features, which can be analyzed as unique HD biomarkers.…”

Section: Discussionmentioning

confidence: 99%

What, When and How to Measure—Peripheral Biomarkers in Therapy of Huntington’s Disease

Przybył

Woźna-Wysocka

Kozłowska

et al. 2021

IJMS

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Among the main challenges in further advancing therapeutic strategies for Huntington’s disease (HD) is the development of biomarkers which must be applied to assess the efficiency of the treatment. HD is a dreadful neurodegenerative disorder which has its source of pathogenesis in the central nervous system (CNS) but is reflected by symptoms in the periphery. Visible symptoms include motor deficits and slight changes in peripheral tissues, which can be used as hallmarks for prognosis of the course of HD, e.g., the onset of the disease symptoms. Knowing how the pathology develops in the context of whole organisms is crucial for the development of therapy which would be the most beneficial for patients, as well as for proposing appropriate biomarkers to monitor disease progression and/or efficiency of treatment. We focus here on molecular peripheral biomarkers which could be used as a measurable outcome of potential therapy. We present and discuss a list of wet biomarkers which have been proposed in recent years to measure pre- and postsymptomatic HD. Interestingly, investigation of peripheral biomarkers in HD can unravel new aspects of the disease pathogenesis. This especially refers to inflammatory proteins or specific immune cells which attract scientific attention in neurodegenerative disorders.

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Section: Discussionmentioning

confidence: 99%

What, When and How to Measure—Peripheral Biomarkers in Therapy of Huntington’s Disease

Przybył

Woźna-Wysocka

Kozłowska

et al. 2021

IJMS

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“…The choice of this disease has been made to illustrate its general properties. The task is to provide a current landscape, largely common to PD [ 21 , 29 , 36 ] but not always to other neurodegenerative diseases (see, for example, [ 9 , 17 , 28 , 31 , 32 ]).…”

Section: Ad and Its Multiple Fluid Biomarkersmentioning

confidence: 99%

“…Initially, each neurodegenerative disease was considered dependent on a single specific biomarker, such as Aβ for AD and α-synuclein for PD. Now it is clear that these two, as well as many other biomarkers, are not fully specific but expressed also by patients of other neurodegenerative diseases [ 9 ]. Multispecificity of biomarkers requires caution in their operation.…”

Section: Introductionmentioning

confidence: 99%

News about the Role of Fluid and Imaging Biomarkers in Neurodegenerative Diseases

Meldolesi

2021

Biomedicines

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Biomarkers are molecules that are variable in their origin, nature, and mechanism of action; they are of great relevance in biology and also in medicine because of their specific connection with a single or several diseases. Biomarkers are of two types, which in some cases are operative with each other. Fluid biomarkers, started around 2000, are generated in fluid from specific proteins/peptides and miRNAs accumulated within two extracellular fluids, either the central spinal fluid or blood plasma. The switch of these proteins/peptides and miRNAs, from free to segregated within extracellular vesicles, has induced certain advantages including higher levels within fluids and lower operative expenses. Imaging biomarkers, started around 2004, are identified in vivo upon their binding by radiolabeled molecules subsequently revealed in the brain by positron emission tomography and/or other imaging techniques. A positive point for the latter approach is the quantitation of results, but expenses are much higher. At present, both types of biomarker are being extensively employed to study Alzheimer’s and other neurodegenerative diseases, investigated from the presymptomatic to mature stages. In conclusion, biomarkers have revolutionized scientific and medical research and practice. Diagnosis, which is often inadequate when based on medical criteria only, has been recently improved by the multiplicity and specificity of biomarkers. Analogous results have been obtained for prognosis. In contrast, improvement of therapy has been limited or fully absent, especially for Alzheimer’s in which progress has been inadequate. An urgent need at hand is therefore the progress of a new drug trial design together with patient management in clinical practice.

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“…Among the informative biological avenues recently investigated in neuromuscular disorders (NMD), the kynurenine (KYN) Pathway (KP) appears as one of the most promising [ 4 , 5 , 6 ]. KP represents the major route of tryptophan (TRP) catabolism to nicotinamide adenine dinucleotide (NAD+) [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Some CSF Kynurenine Pathway Intermediates Associated with Disease Evolution in Amyotrophic Lateral Sclerosis

et al. 2021

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The aim of this study was to evaluate the kynurenine pathway (KP) and amino acids profile, using mass spectrometry, in the cerebrospinal fluid (CSF) of 42 amyotrophic lateral sclerosis (ALS) patients at the diagnosis and 40 controls to detect early disorders of these pathways. Diagnostic and predictive ability (based on weight loss, forced vital capacity, ALS Functional Rating Scale—Revised evolution over 12 months, and survival time) of these metabolites were evaluated using univariate followed by supervised multivariate analysis. The multivariate model between ALS and controls was not significant but highlighted some KP metabolites (kynurenine (KYN), kynurenic acid (KYNA), 3-Hydroxynurenine (3-HK)/KYNA ratio), and amino acids (Lysine, asparagine) as involved in the discrimination between groups (accuracy 62%). It revealed a probable KP impairment toward neurotoxicity in ALS patients and in bulbar forms. Regarding the prognostic effect of metabolites, 12 were commonly discriminant for at least 3 of 4 disease evolution criteria. This investigation was crucial as it did not show significant changes in CSF concentrations of amino acids and KP intermediates in early ALS evolution. However, trends of KP modifications suggest further exploration. The unclear kinetics of neuroinflammation linked to KP support the interest in exploring these pathways during disease evolution through a longitudinal strategy.

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Searching for Peripheral Biomarkers in Neurodegenerative Diseases: The Tryptophan-Kynurenine Metabolic Pathway

Cited by 104 publications

References 151 publications

What, When and How to Measure—Peripheral Biomarkers in Therapy of Huntington’s Disease

What, When and How to Measure—Peripheral Biomarkers in Therapy of Huntington’s Disease

News about the Role of Fluid and Imaging Biomarkers in Neurodegenerative Diseases

Some CSF Kynurenine Pathway Intermediates Associated with Disease Evolution in Amyotrophic Lateral Sclerosis

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