Dated: Jun 01, 2022
Publication Name: Current Opinion in Biotechnology
Citations : Neurotoxicity of phenylalanine on human iPSC-derived cerebral organoids
Phenylketonuria (PKU) is a common genetic metabolic disorder that causes phenylalanine accumulation in the blood. The most serious symptoms are related to the brain, as intellectual disability, seizure, and microcephaly are commonly found in poorly treated PKU patients and the babies of maternal PKU. However, the mechanism of hyperphenylalaninemia on human neurodevelopment is still unclear. Here we utilized human induced pluripotent stem cell (iPSC)-derived cerebral organoids to investigate the neurotoxicity of hyperphenylalaninemia. Cerebral organoids at days 40 or 100 were treated with different concentrations of phenylalanine for 5 days. After phenylalanine treatments, the cerebral organoids displayed alterations in organoid size, induction of apoptosis, and depletion of neural progenitor cells. These findings indicate that phenylalanine exposure may contribute to microcephaly, abnormal cortical expansion, and myelination lesions in the developing human brain.
Contributors: Jieun Kim, Seungbok Lee, Jaemeun Lee, Jong-Chan Park, Kyung Hyun Kim, Jung Min Ko, Sun-Hyun Park, Seung-Ki Kim, Inhee Mook-Jung, Ji Yeoun Lee