Oxidative stress in phenylketonuria-evidence from human studies and animal models, and possible implications for redox signaling
| Autor: | Clovis Milton Duval Wannmacher, Vanessa Trindade Bortoluzzi, Carlos Severo Dutra Filho |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
congenital hereditary and neonatal diseases and abnormalities medicine.medical_specialty Neurology Low protein Diet therapy Bioinformatics medicine.disease_cause Biochemistry Antioxidants 03 medical and health sciences Cellular and Molecular Neuroscience Epilepsy 0302 clinical medicine Phenylketonurias Intellectual disability Medicine Animals Humans Clinical significance business.industry nutritional and metabolic diseases Brain medicine.disease Disease Models Animal Oxidative Stress 030104 developmental biology Anxiety Neurology (clinical) medicine.symptom business Oxidation-Reduction 030217 neurology & neurosurgery Oxidative stress Signal Transduction |
| Zdroj: | Metabolic brain disease. 36(4) |
| ISSN: | 1573-7365 |
| Popis: | Phenylketonuria (PKU) is one of the commonest inborn error of amino acid metabolism. Before mass neonatal screening was possible, and the success of introducing diet therapy right after birth, the typical clinical finds in patients ranged from intellectual disability, epilepsy, motor deficits to behavioral disturbances and other neurological and psychiatric symptoms. Since early diagnosis and treatment became widespread, usually only those patients who do not strictly follow the diet present psychiatric, less severe symptoms such as anxiety, depression, sleep pattern disturbance, and concentration and memory problems. Despite the success of low protein intake in preventing otherwise severe outcomes, PKU's underlying neuropathophysiology remains to be better elucidated. Oxidative stress has gained acceptance as a disturbance implicated in the pathogenesis of PKU. The conception of oxidative stress has evolved to comprehend how it could interfere and ultimately modulate metabolic pathways regulating cell function. We summarize the evidence of oxidative damage, as well as compromised antioxidant defenses, from patients, animal models of PKU, and in vitro experiments, discussing the possible clinical significance of these findings. There are many studies on oxidative stress and PKU, but only a few went further than showing macromolecular damage and disturbance of antioxidant defenses. In this review, we argue that these few studies may point that oxidative stress may also disturb redox signaling in PKU, an aspect few authors have explored so far. The reported effect of phenylalanine on the expression or activity of enzymes participating in metabolic pathways known to be responsive to redox signaling might be mediated through oxidative stress. |
| Databáze: | OpenAIRE |
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