News Releases & Research Results Elucidation of the molecular brain pathology of neuropsychiatric disorders due to 22q11.2 deletion syndrome using iPS cells

The results of the research project conducted by Specially Appointed Lecturer Yuko Arioka of the Department of Advanced Medicine, Nagoya University Hospital/Department of Psychiatry, Graduate School of Medicine, Nagoya University and Professor Norio Ozaki of the Department of Psychiatry, Graduate School of Medicine, Nagoya University.

• The molecular brain pathology of 22q11.2 deletion syndrome (*), one of the designated intractable diseases, was successfully elucidated by analysis with iPS cells.
  (*) 22q11.2 deletion syndrome is a designated intractable disease, included in chromosomal microdeletion syndrome, with an incidence of 1 in 4,000. Although those with 22q11.2 deletion syndrome can survive after heart surgery, about 90% of them are at a higher risk of developing various neuropsychiatric disorders, including neurological degenerative disorders, such as juvenile Parkinson's disease, as well as psychiatric disorders such as intellectual disability, autism spectrum disorder, and schizophrenia.
• Specifically, dopamine neurons were prepared from established iPS cells to comprehensively compare protein expressions between patients with 22q11.2 deletion syndrome and healthy individuals, demonstrating the reduced expressions of proteins involved in endoplasmic reticulum functions, especially, marked dysfunction of a protein called "PERK” in the patients.
• The results of this research should promote the development of therapeutic agents for neuropsychiatric disorders in patients with 22q11.2 deletion syndrome and the prevention of their onset in the future.

This project was conducted with the support of the Brain Mapping by Integrated Neurotechnologies for Disease Studies (Brain/MINDS) by AMED.

The results of this research project were published in EBioMedicine on December 18.

Arioka Y., et al. Chromosome 22q11.2 deletion causes PERK-dependent vulnerability in dopaminergic neurons EBioMedicine
DOI: 10.1016/j.ebiom.2020.103138