Is monoamine oxydase-B a modifying gene and phenylethylamine a harmful compound in phenylketonuria?

Ghozlan, A.; Varoquaux, O; Abadie, Véronique

doi:10.1016/j.ymgme.2004.07.004

Cited by 10 publications

(5 citation statements)

References 9 publications

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“…The outcomes are usually severe when this metabolic disease is left untreated; however, white matter pathology is common even in early diagnosed and treated individuals. Multiple mechanisms by which Phe induces its deleterious effects on brain include impairment of large neutral amino acids (LNAA) uptake into brain, reduction of the availability for neurotransmitters synthesis, inhibition of key enzymatic activities, reduction of the activity of monoamine oxidase B as modifying gene and alteration on myelin metabolism (Ghozlan et al, 2004; Anderson et al, 2007; Blau et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Urinary biomarkers of oxidative stress and plasmatic inflammatory profile in phenylketonuric treated patients

Deon

Sitta²,

Faverzani³

et al. 2015

Intl J of Devlp Neuroscience

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Oxidative stress has been proposed as an important pathophysiologic feature of various inborn errors of metabolism, including phenylketonuria (PKU). Considering that there are few studies relating oxidative stress and inflammation directly in PKU disease, the aim of this study was to evaluate and correlate oxidative damage to biomolecules, antioxidant defenses, pro-inflammatory cytokines, phenylalanine (Phe) and its metabolites (phenyllactic acid--PLA and phenylacetic acid--PAA) levels in urine and plasma from patients with PKU under dietary treatment. We observed a marked increase of isoprostanes, which is a lipid peroxidation biomarker, in urine from these treated patients. Next, we demonstrated that protein oxidative damage, measured by di-tyrosine formation, was significantly increased in urine from PKU treated patients and that decreased urinary antioxidant capacity was also observed. Our findings concerning to the inflammatory cytokines interleukin-6 and interleukin-1β, both significantly increased in these patients, provide evidence that the pro-inflammatory state occurs. Besides, interleukin-1β was positively correlated with isoprostanes. We observed a negative correlation between interleukin-6 and interleukin-10, an anti-inflammatory cytokine. Di-tyrosine was positively correlated with Phe, which indicates oxidative damage to proteins, as well as with PAA. These findings may suggest that the protein damage may be induced by Phe and its metabolite PAA in PKU. Our results indicate that pro-oxidant and pro-inflammatory states occur and are, in part, correlated and protein oxidation seems to be induced by Phe and PPA in PKU patients.

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Section: Introductionmentioning

confidence: 99%

Urinary biomarkers of oxidative stress and plasmatic inflammatory profile in phenylketonuric treated patients

Deon

Sitta²,

Faverzani³

et al. 2015

Intl J of Devlp Neuroscience

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“…Modifier genes frequently contribute to the phenotype in autosomal recessive disorders. For example, monoamine oxidase type B ( MOAB ) is a modifier gene in phenylketonuria [Ghozlan et al, 2004], and polymorphisms of both mannose-binding lectin2 ( MBL2 ) and transforming growth factor beta 1 ( TGFβ1 ) influence pulmonary outcome in cystic fibrosis [Accurso and Sontag, 2008]. This study was conducted to investigate the impact of potential modifier genes on NPC severity.…”

Section: Introductionmentioning

confidence: 99%

Apolipoprotein E genotype and neurological disease onset in Niemann–Pick disease, type C1

Fu¹,

Yanjanin²,

Elrick³

et al. 2012

American J of Med Genetics Pt A

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Niemann-Pick disease, type C1 (NPC1) is a lipid storage disorder that results in progressive neurological impairment. The NPC1 phenotype is extremely variable and at the individual level is likely influenced by other genetic traits. In addition to residual function of NPC1 protein, we hypothesize that modifier genes, as frequently observed with other autosomal recessive diseases, influence the NPC phenotype. The NPC1 phenotype includes progressive dementia, and the NPC pathology has some overlap with the pathology of Alzheimer disease. Thus, we examined apolipoprotein E (ApoE) and microtubule associated protein tau (MAPT) polymorphisms in a cohort of 15 NPC1 patients with well characterized longitudinal disease progression. Although we did not find any correlations between disease severity and Tau polymorphisms, we found significant associations between ApoE polymorphisms and phenotypic severity. Specifically, ApoE4 and ApoE2 alleles were associated, respectively, with increased and decreased disease severity in this cohort of NPC1 patients. These data support the hypothesis that ApoE may play a role in modulating NPC1 neuropathology.

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“…MAO enzymes have been linked to neuro-inflammation and oxidative stress as a result of their activity which generates hydrogen peroxide and ammonia as byproducts. It has been reported that newborns have low MAO-B activity and act as a modifying gene in phenylketonuria (33). Discussion has been limited because measurement of MAO activity in the PKU model has not been previously reported.…”

Section: Discussionmentioning

confidence: 99%

Rat PKU Model Display Gender-Based Neuroinflammatory Changes: Proinflamatuary Cytokines and Lipid Peroxidation

Çiçek,

Gök,

Bodur

2024

Muğla Sıtkı Koçman Üniversitesi Tıp Dergisi

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Phenylketonuria (PKU) results from congenital defects of amino acid metabolism. Accumulated phenylalanine crosses the blood-brain barrier and causes permanent brain damage, but the neuro-pathophysiology underlying phenylketonuria is not fully understood. Chemically-induced rat phenylketonuria model of both genders was generated to examine the role of inflammatory response, lipid peroxidation and oxidative stress in the prefrontal cortex. Our results showed that in phenylketonuria there was an increase in lipid peroxidation compared to controls, which was significantly different only in males (p

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Is monoamine oxydase-B a modifying gene and phenylethylamine a harmful compound in phenylketonuria?

Cited by 10 publications

References 9 publications

Urinary biomarkers of oxidative stress and plasmatic inflammatory profile in phenylketonuric treated patients

Urinary biomarkers of oxidative stress and plasmatic inflammatory profile in phenylketonuric treated patients

Apolipoprotein E genotype and neurological disease onset in Niemann–Pick disease, type C1

Rat PKU Model Display Gender-Based Neuroinflammatory Changes: Proinflamatuary Cytokines and Lipid Peroxidation

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