scholarly journals Understanding the Roles of the Kynurenine Pathway in Multiple Sclerosis Progression

2010 ◽  
Vol 3 ◽  
pp. IJTR.S4294 ◽  
Author(s):  
Chai K. Lim ◽  
Bruce J. Brew ◽  
Gayathri Sundaram ◽  
Gilles J. Guillemin
Keyword(s):  
Multiple Sclerosis ◽  
Nicotinamide Adenine Dinucleotide ◽  
Brain Tumours ◽  
Therapeutic Strategy ◽  
Inflammatory Diseases ◽  
Kynurenine Pathway ◽  
Aids Dementia Complex ◽  
Regulatory Mechanisms ◽  
Aids Dementia ◽  
Lateral Sclerosis

The kynurenine pathway (KP) is a major degradative pathway of tryptophan ultimately leading to the production of nicotinamide adenine dinucleotide (NAD+) and is also one of the major regulatory mechanisms of the immune response. The KP is known to be involved in several neuroinflammatory disorders including Alzheimer's disease, amyotrophic lateral sclerosis, AIDS dementia complex, Parkinson's disease, schizophrenia, Huntington's disease and brain tumours. However, the KP remains a relatively new topic for the field of multiple sclerosis (MS). Over the last 2–3 years, some evidence has progressively emerged suggesting that the KP is likely to be involved in the pathogenesis of autoimmune diseases especially MS. Some KP modulators are already in clinical trials for other inflammatory diseases and would potentially provide a new and important therapeutic strategy for MS patients. This review summarizes the known relationships between the KP and MS.

scholarly journals Kynurenine Pathway Metabolites in Humans: Disease and Healthy States

2009 ◽  
Vol 2 ◽  
pp. IJTR.S2097 ◽  
Author(s):  
Yiquan Chen ◽  
Gilles J. Guillemin
Keyword(s):  
Immune Response ◽  
Essential Amino Acid ◽  
Kynurenic Acid ◽  
Biological Significance ◽  
Kynurenine Pathway ◽  
Aids Dementia Complex ◽  
Aids Dementia ◽  
Major Route ◽  
Inflammatory Molecules ◽  
Lateral Sclerosis

Tryptophan is an essential amino acid that can be metabolised through different pathways, a major route being the kynurenine pathway. The first enzyme of the pathway, indoleamine-2,3-dioxygenase, is strongly stimulated by inflammatory molecules, particularly interferon gamma. Thus, the kynurenine pathway is often systematically up-regulated when the immune response is activated. The biological significance is that 1) the depletion of tryptophan and generation of kynurenines play a key modulatory role in the immune response; and 2) some of the kynurenines, such as quinolinic acid, 3-hydroxykynurenine and kynurenic acid, are neuroactive. The kynurenine pathway has been demonstrated to be involved in many diseases and disorders, including Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease, AIDS dementia complex, malaria, cancer, depression and schizophrenia, where imbalances in tryptophan and kynurenines have been found. This review compiles most of these studies and provides an overview of how the kynurenine pathway might be contributing to disease development, and the concentrations of tryptophan and kynurenines in the serum, cerebrospinal fluid and brain tissues in control and patient subjects.

scholarly journals Friends or Foes: Matrix Metalloproteinases and Their Multifaceted Roles in Neurodegenerative Diseases

2015 ◽  
Vol 2015 ◽  
pp. 1-27 ◽  
Author(s):  
Marjana Brkic ◽  
Sriram Balusu ◽  
Claude Libert ◽  
Roosmarijn E. Vandenbroucke
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Matrix Metalloproteinases ◽  
Neurodegenerative Diseases ◽  
Therapeutic Strategy ◽  
Pathological Conditions ◽  
Progressive Loss ◽  
Neuro Inflammation ◽  
Potential Use ◽  
Lateral Sclerosis

Neurodegeneration is a chronic progressive loss of neuronal cells leading to deterioration of central nervous system (CNS) functionality. It has been shown that neuroinflammation precedes neurodegeneration in various neurodegenerative diseases. Matrix metalloproteinases (MMPs), a protein family of zinc-containing endopeptidases, are essential in (neuro)inflammation and might be involved in neurodegeneration. Although MMPs are indispensable for physiological development and functioning of the organism, they are often referred to as double-edged swords due to their ability to also inflict substantial damage in various pathological conditions. MMP activity is strictly controlled, and its dysregulation leads to a variety of pathologies. Investigation of their potential use as therapeutic targets requires a better understanding of their contributions to the development of neurodegenerative diseases. Here, we review MMPs and their roles in neurodegenerative diseases: Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), Huntington’s disease (HD), and multiple sclerosis (MS). We also discuss MMP inhibition as a possible therapeutic strategy to treat neurodegenerative diseases.

scholarly journals Kynurenines in the Pathogenesis of Multiple Sclerosis: Therapeutic Perspectives

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1564 ◽  
Author(s):  
Tamás Biernacki ◽  
Dániel Sandi ◽  
Krisztina Bencsik ◽  
László Vécsei
Keyword(s):  
Multiple Sclerosis ◽  
Immune System ◽  
Quinolinic Acid ◽  
Nicotinamide Adenine Dinucleotide ◽  
Kynurenic Acid ◽  
Picolinic Acid ◽  
Kynurenine Pathway ◽  
Current Evidence ◽  
Therapeutic Approaches ◽  
The Past

Over the past years, an increasing amount of evidence has emerged in support of the kynurenine pathway’s (KP) pivotal role in the pathogenesis of several neurodegenerative, psychiatric, vascular and autoimmune diseases. Different neuroactive metabolites of the KP are known to exert opposite effects on neurons, some being neuroprotective (e.g., picolinic acid, kynurenic acid, and the cofactor nicotinamide adenine dinucleotide), while others are toxic to neurons (e.g., 3-hydroxykynurenine, quinolinic acid). Not only the alterations in the levels of the metabolites but also disturbances in their ratio (quinolinic acid/kynurenic acid) have been reported in several diseases. In addition to the metabolites, the enzymes participating in the KP have been unearthed to be involved in modulation of the immune system, the energetic upkeep of neurons and have been shown to influence redox processes and inflammatory cascades, revealing a sophisticated, intertwined system. This review considers various methods through which enzymes and metabolites of the kynurenine pathway influence the immune system, the roles they play in the pathogenesis of neuroinflammatory diseases based on current evidence with a focus on their involvement in multiple sclerosis, as well as therapeutic approaches.

Cerebrospinal fluid beta-2-microglobulin in multiple sclerosis and AIDS dementia complex

1992 ◽  
Vol 14 (3) ◽  
pp. 282-283 ◽  
Author(s):  
P.B. Carrieri ◽  
A. Indaco ◽  
A. Maiorino ◽  
G.A. Buscaino ◽  
A. Ponticiello ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Aids Dementia Complex ◽  
Aids Dementia ◽  
Beta 2 ◽  
Beta 2 Microglobulin

scholarly journals Occupational Therapy Interventions in Adults with Multiple Sclerosis or Amyotrophic Lateral Sclerosis: A Scoping Review

2021 ◽  
Vol 18 (4) ◽  
pp. 1432
Author(s):  
Luis De-Bernardi-Ojuel ◽  
Laura Torres-Collado ◽  
Manuela García-de-la-Hera
Keyword(s):  
Multiple Sclerosis ◽  
Amyotrophic Lateral Sclerosis ◽  
Occupational Therapy ◽  
Scoping Review ◽  
Adult Population ◽  
Falls Prevention ◽  
Targeted Interventions ◽  
Therapy Interventions ◽  
Occupational Therapy Interventions ◽  
Lateral Sclerosis

This scoping review aims to describe occupational therapy interventions carried out with multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS) patients in occupational therapy. A peer review of the literature was conducted in different databases: Pubmed, Scopus, Web of Science and Embase, and in some occupational therapy journals. A search of the literature published was carried out before December 2019. The inclusion criteria were as follows: (1) articles evaluating the intervention of occupational therapy in MS or ALS including experimental, randomized, nonrandomized and exploratory studies; (2) written in English or Spanish; (3) adult population (over 18 years old). The initial search identified 836 articles of which we included 32 divided into four areas of intervention: fatigue-targeted interventions, cognitive interventions, physical interventions and others. Only 16 studies were carried out exclusively by occupational therapists. Most occupational therapy interventions are aimed at fatigue and physical rehabilitation. The majority of the studies in our review included MS patients, with little representation from the ALS population. These interventions have shown an improvement in perceived fatigue, manual dexterity, falls prevention and improvement in cognitive aspects such as memory, communication, depression and quality of life in the MS and ALS populations.

Targeting SHP2 as a therapeutic strategy for inflammatory diseases

2021 ◽  
Vol 214 ◽  
pp. 113264
Author(s):  
Yang Liu ◽  
Xiaohe Yang ◽  
Yali Wang ◽  
Yueying Yang ◽  
Dejuan Sun ◽  
...  
Keyword(s):  
Therapeutic Strategy ◽  
Inflammatory Diseases

scholarly journals Paraoxonase Role in Human Neurodegenerative Diseases

Antioxidants ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 11
Author(s):  
Cadiele Oliana Reichert ◽  
Debora Levy ◽  
Sergio P. Bydlowski
Keyword(s):  
Oxidative Stress ◽  
Multiple Sclerosis ◽  
Amyotrophic Lateral Sclerosis ◽  
Neurodegenerative Diseases ◽  
High Density Lipoprotein ◽  
Density Lipoprotein ◽  
Structural Homology ◽  
Redox Systems ◽  
Genetic Cluster ◽  
Lateral Sclerosis

The human body has biological redox systems capable of preventing or mitigating the damage caused by increased oxidative stress throughout life. One of them are the paraoxonase (PON) enzymes. The PONs genetic cluster is made up of three members (PON1, PON2, PON3) that share a structural homology, located adjacent to chromosome seven. The most studied enzyme is PON1, which is associated with high density lipoprotein (HDL), having paraoxonase, arylesterase and lactonase activities. Due to these characteristics, the enzyme PON1 has been associated with the development of neurodegenerative diseases. Here we update the knowledge about the association of PON enzymes and their polymorphisms and the development of multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), Alzheimer’s disease (AD) and Parkinson’s disease (PD).

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