論文種別	原著(症例報告除く)
言語種別	英語
査読の有無	その他(不明)
表題	Neurogenesis defects in iPSC-derived midbrain organoids of early-onset Parkinson's disease with 22q11.2 deletion syndrome.
掲載誌名	正式名：Frontiers in cellular neuroscience 略　 称：Front Cell Neurosci ISSNコード：16625102/16625102
掲載区分	国外
巻・号・頁	20,pp.1906023
著者・共著者	Syugo Ueki, Toshiya Kimura, Rie Tohge, Atsushi Tamada, Mitsuaki Oki, Yusuke Yakushiji, Haruhisa Inoue, Satoshi Kaneko, Keiko Muguruma
発行年月	2026/07
概要	Sporadic Parkinson's disease (PD) is typically a late-onset disorder caused by a combination of genetics, environment, and aging, manifesting when the loss of midbrain dopaminergic neurons exceeds a critical threshold, usually after the age of 50. Conversely, early-onset PD, as observed in cases linked to parkin (PRKN) gene mutations, suggests mechanisms involving either accelerated postnatal neuron loss or an insufficient number of neurons at birth. Patients with the 22q11.2 deletion syndrome (DS) have a significantly higher prevalence of early-onset PD. The absence of known genes associated with hereditary PD in the deleted region suggests the involvement of novel, non-traditional risk factors. This could potentially implicate the neurodevelopmental origin of dopaminergic neurons arising from the floor plate. To investigate this hypothesis, we generated midbrain organoids from induced pluripotent stem cells derived from a patient with 22q11.2 DS. The organoids recapitulated key aspects of in vivo neurogenesis, revealing enhanced differentiation of dopaminergic neurons in 22q11.2DS- and PRKN-derived organoids compared to controls on days 28 and 56 of culture. These findings suggest that, in early-onset PD patients with 22q11.2 DS or PRKN mutation, enhanced neurogenesis could result in reduced number of dopaminergic neurons during early development. The organoids of early-onset PD demonstrated that progenitors undergo enhanced differentiation at an early stage. This suggests that the atypical developmental process could reduce progenitors before there are enough mature dopaminergic neurons. This in turn indicates that the onset of PD may occur as early as the embryonic stage.
DOI	10.3389/fncel.2026.1906023
PMID	42601939