@article{5c1aa4fde5874d649cb94a83f6e0c9da,
title = "Engineering Organoids for in vitro Modeling of Phenylketonuria",
abstract = "Phenylketonuria is a recessive genetic disorder of amino-acid metabolism, where impaired phenylalanine hydroxylase function leads to the accumulation of neurotoxic phenylalanine levels in the brain. Severe cognitive and neuronal impairment are observed in untreated/late-diagnosed patients, and even early treated ones are not safe from life-long sequelae. Despite the wealth of knowledge acquired from available disease models, the chronic effect of Phenylketonuria in the brain is still poorly understood and the consequences to the aging brain remain an open question. Thus, there is the need for better predictive models, able to recapitulate specific mechanisms of this disease. Human induced pluripotent stem cells (hiPSCs), with their ability to differentiate and self-organize in multiple tissues, might provide a new exciting in vitro platform to model specific PKU-derived neuronal impairment. In this review, we gather what is known about the impact of phenylalanine in the brain of patients and highlight where hiPSC-derived organoids could contribute to the understanding of this disease.",
keywords = "disease modeling, human induced pluripotent stem cells, neurodegeneration, neurodevelopment, organoids, phenylketonuria",
author = "Borges, {Alice C.} and Kerensa Broersen and Paula Leandro and Fernandes, {Tiago G.}",
note = "Funding Information: This work was supported by Portuguese national funds from FCT—Funda{\c c}{\~a}o para a Ci{\^e}ncia e a Tecnologia, I.P., in the scope of the project UIDB/04565/2020 and UIDP/04565/2020 of the Research Unit Institute for Bioengineering and Biosciences (iBB) and the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy (i4HB), and UIDB/04138/2020 and UIDP/04138/2020 of the Research Institute for Medicines (iMed.ULisboa). We also acknowledge FCT funding through project CEREBEX Generation of Cerebellar Organoids for Ataxia, Research grant LISBOA-01-0145-FEDER-029298. The work in Broersen{\textquoteright}s lab on organoids was supported by the Dutch Research Council (NWO)-Gravitation grant “Netherlands Organ-on-Chip Initiative” 024.003.001. Funding Information: This work was supported by Portuguese national funds from FCT?Funda??o para a Ci?ncia e a Tecnologia, I.P., in the scope of the project UIDB/04565/2020 and UIDP/04565/2020 of the Research Unit Institute for Bioengineering and Biosciences (iBB) and the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy (i4HB), and UIDB/04138/2020 and UIDP/04138/2020 of the Research Institute for Medicines (iMed.ULisboa). We also acknowledge FCT funding through project CEREBEX Generation of Cerebellar Organoids for Ataxia, Research grant LISBOA-01-0145-FEDER-029298. The work in Broersen?s lab on organoids was supported by the Dutch Research Council (NWO)-Gravitation grant ?Netherlands Organ-on-Chip Initiative? 024.003.001. Publisher Copyright: Copyright {\textcopyright} 2022 Borges, Broersen, Leandro and Fernandes.",
year = "2022",
month = jan,
day = "10",
doi = "10.3389/fnmol.2021.787242",
language = "English",
volume = "14",
journal = "Frontiers in Molecular Neuroscience",
issn = "1662-5099",
publisher = "Frontiers Research Foundation",
}