2022
DOI: 10.1038/s41536-022-00252-5
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Modelling urea cycle disorders using iPSCs

Abstract: The urea cycle is a liver-based pathway enabling disposal of nitrogen waste. Urea cycle disorders (UCDs) are inherited metabolic diseases caused by deficiency of enzymes or transporters involved in the urea cycle and have a prevalence of 1:35,000 live births. Patients present recurrent acute hyperammonaemia, which causes high rate of death and neurological sequelae. Long-term therapy relies on a protein-restricted diet and ammonia scavenger drugs. Currently, liver transplantation is the only cure. Hence, high … Show more

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Cited by 14 publications
(21 citation statements)
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“…Low concentrations of BCAAs are related to suppression in albumin synthesis and its decreased secretion as well as chronic liver disease [ 35 , 36 ]. In addition, urea showed a significant decrease in the HBB-exposed and chronic toxicity groups, which could indicate HBB triggered an abnormal urea cycle activity for processing excess nitrogen mainly generated by ammonia within the liver [ 37 ]. Accumulation of ammonia induces oxidative/nitrosative stress in astrocytes and is known to cause neurotoxicity [ 38 ].…”
Section: Discussionmentioning
confidence: 99%
“…Low concentrations of BCAAs are related to suppression in albumin synthesis and its decreased secretion as well as chronic liver disease [ 35 , 36 ]. In addition, urea showed a significant decrease in the HBB-exposed and chronic toxicity groups, which could indicate HBB triggered an abnormal urea cycle activity for processing excess nitrogen mainly generated by ammonia within the liver [ 37 ]. Accumulation of ammonia induces oxidative/nitrosative stress in astrocytes and is known to cause neurotoxicity [ 38 ].…”
Section: Discussionmentioning
confidence: 99%
“…Developing alternatives models with induced pluripotent stem cells derived neurons or neuronal or organotypic cultures will provide surrogates to better study the complex pathophysiology of this disorder. 49,50…”
Section: Discussionmentioning
confidence: 99%
“…Analysing metabolites from cerebrospinal fluid and MRI spectroscopy with prospective monitoring will provide better tools to understand the pathophysiology of the epilepsy and neurological disease in ASA. Developing alternatives models with induced pluripotent stem cells derived neurons or neuronal or organotypic cultures will provide surrogates to better study the complex pathophysiology of this disorder (43,44).…”
Section: Discussionmentioning
confidence: 99%