Memantine and Kynurenic Acid: Current Neuropharmacological Aspects

Majláth, Zsófia; Török, Nóra; Toldi, József; Vécsei, László

doi:10.2174/1570159x14666151113123221

Cited by 45 publications

(24 citation statements)

References 107 publications

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“…Kynurenine can be further catabolized into various downstream products such as kynurenic acid (KYNA). This metabolite is well-known for its neuroprotective role in the central nervous system (CNS) because of its antagonism of glutamate receptors such as the NMDA, AMPA, and kainate receptors [26]. Thus, increased KYNA levels are associated with amelioration of the excitotoxic conditions seen in age-related disorders like Alzheimer's (AD) and Parkinson's disease.…”

Section: Kynurenic Acid Antagonizes Nmda Receptors Found On Osteoclastsmentioning

confidence: 99%

The Role of Tryptophan Metabolites in Musculoskeletal Stem Cell Aging

Anaya

Bollag

Hamrick

et al. 2020

IJMS

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Although aging is considered a normal process, there are cellular and molecular changes that occur with aging that may be detrimental to health. Osteoporosis is one of the most common age-related degenerative diseases, and its progression correlates with aging and decreased capacity for stem cell differentiation and proliferation in both men and women. Tryptophan metabolism through the kynurenine pathway appears to be a key factor in promoting bone-aging phenotypes, promoting bone breakdown and interfering with stem cell function and osteogenesis; however, little data is available on the impact of tryptophan metabolites downstream of kynurenine. Here we review available data on the impact of these tryptophan breakdown products on the body in general and, when available, the existing evidence of their impact on bone. A number of tryptophan metabolites (e.g., 3-hydroxykynurenine (3HKYN), kynurenic acid (KYNA) and anthranilic acid (AA)) have a detrimental effect on bone, decreasing bone mineral density (BMD) and increasing fracture risk. Other metabolites (e.g., 3-hydroxyAA, xanthurenic acid (XA), picolinic acid (PIA), quinolinic acid (QA), and NAD+) promote an increase in bone mineral density and are associated with lower fracture risk. Furthermore, the effects of other tryptophan breakdown products (e.g., serotonin) are complex, with either anabolic or catabolic actions on bone depending on their source. The mechanisms involved in the cellular actions of these tryptophan metabolites on bone are not yet fully known and will require further research as they are potential therapeutic targets. The current review is meant as a brief overview of existing English language literature on tryptophan and its metabolites and their effects on stem cells and musculoskeletal systems. The search terms used for a Medline database search were: kynurenine, mesenchymal stem cells, bone loss, tryptophan metabolism, aging, and oxidative stress.

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Section: Kynurenic Acid Antagonizes Nmda Receptors Found On Osteoclastsmentioning

confidence: 99%

The Role of Tryptophan Metabolites in Musculoskeletal Stem Cell Aging

Anaya

Bollag

Hamrick

et al. 2020

IJMS

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“…KYNA concentration is increased in the prefrontal cortex of people with schizophrenia; KYNA concentration correlated with dopamine, acetylcholine and glutamate levels which reflect the degree of cognitive impairment ( Petrova and Dorofeykova, 2014 ). KYNA may be a valuable candidate for future therapeutic discovery for the treatment of neurodegenerative diseases ( Majláth et al, 2016 ) such as schizophrenia.…”

Section: Pathophysiology Of Kynurenine Pathway In Schizophreniamentioning

confidence: 99%

Kynurenine pathway and cognitive impairments in schizophrenia: Pharmacogenetics of galantamine and memantine

Koola

2016

Schizophrenia Research: Cognition

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The Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) project designed to facilitate the development of new drugs for the treatment of cognitive impairments in people with schizophrenia, identified three drug mechanisms of particular interest: dopaminergic, cholinergic, and glutamatergic. Galantamine is an acetylcholinesterase inhibitor and a positive allosteric modulator of the α7 nicotinic receptors. Memantine is an N-methyl-D-aspartate (NMDA) receptor antagonist. There is evidence to suggest that the combination of galantamine and memantine may be effective in the treatment of cognitive impairments in schizophrenia. There is a growing body of evidence that excess kynurenic acid (KYNA) is associated with cognitive impairments in schizophrenia. The α-7 nicotinic and the NMDA receptors may counteract the effects of kynurenic acid (KYNA) resulting in cognitive enhancement. Galantamine and memantine through its α-7 nicotinic and NMDA receptors respectively may counteract the effects of KYNA thereby improving cognitive impairments. The Single Nucleotide Polymorphisms in the Cholinergic Receptor, Nicotinic, Alpha 7 gene (CHRNA7), Glutamate (NMDA) Receptor, Metabotropic 1 (GRM1) gene, Dystrobrevin Binding Protein 1 (DTNBP1) and kynurenine 3-monooxygenase (KMO) gene may predict treatment response to galantamine and memantine combination for cognitive impairments in schizophrenia in the kynurenine pathway.

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“…Numerous data support the role of kynurenines in neurological diseases, including PD (Bohár et al 2015;Majláth et al 2016b;Klivényi et al 2004;Vécsei et al 2013;Zádori et al 2012b). One of the most important compounds of this system is kynurenic acid (KYNA) (Sas et al 2007).…”

Section: Kynureninesmentioning

confidence: 99%

Neuroprotection in Parkinson’s disease: facts and hopes

et al. 2019

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Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. Behind the symptoms there is a complex pathological mechanism which leads to a dopaminergic cell loss in the substantia nigra pars compacta. Despite the strong efforts, curative treatment has not been found yet. To prevent a further cell death, numerous molecules were tested in terms of neuroprotection in preclinical (in vitro, in vivo) and in clinical studies as well. The aim of this review article is to summarize our knowledge about the extensively tested neuroprotective agents (Search period: 1991-2019). We detail the underlying pathological mechanism and summarize the most important results of the completed animal and clinical trials. Although many positive results have been reported in the literature, there is still no evidence that any of them should be used in clinical practice (Cochrane analysis was performed). Therefore, further studies are needed to better understand the pathomechanism of PD and to find the optimal neuroprotective agent(s).

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Memantine and Kynurenic Acid: Current Neuropharmacological Aspects

Cited by 45 publications

References 107 publications

The Role of Tryptophan Metabolites in Musculoskeletal Stem Cell Aging

The Role of Tryptophan Metabolites in Musculoskeletal Stem Cell Aging

Kynurenine pathway and cognitive impairments in schizophrenia: Pharmacogenetics of galantamine and memantine

Neuroprotection in Parkinson’s disease: facts and hopes

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