Iroquois Homeobox Protein 2 Identified as a Potential Biomarker for Parkinson’s Disease
Open Access
- 14 May 2020
- journal article
- research article
- Published by MDPI AG in International Journal of Molecular Sciences
- Vol. 21 (10), 3455
- https://doi.org/10.3390/ijms21103455
Abstract
The diagnosis of Parkinson’s disease (PD) is initiated after the occurrence of motor symptoms, such as resting tremors, rigidity, and bradykinesia. According to previous reports, non-motor symptoms, notably gastrointestinal dysfunction, could potentially be early biomarkers in PD patients as such symptoms occur earlier than motor symptoms. However, connecting PD to the intestine is methodologically challenging. Thus, we generated in vitro human intestinal organoids from PD patients and ex vivo mouse small intestinal organoids from aged transgenic mice. Both intestinal organoids (IOs) contained the human LRRK2 G2019S mutation, which is the most frequent genetic cause of familial and sporadic PD. By conducting comprehensive genomic comparisons with these two types of IOs, we determined that a particular gene, namely, Iroquois homeobox protein 2 (IRX2), showed PD-related expression patterns not only in human pluripotent stem cell (PSC)-derived neuroectodermal spheres but also in human PSC-derived neuronal cells containing dopaminergic neurons. We expected that our approach of using various cell types presented a novel technical method for studying the effects of multi-organs in PD pathophysiology as well as for the development of diagnostic markers for PD.Funding Information
- National Research Foundation of Korea (2015M3A9C7030128)
- Korea Research Institute of Bioscience and Biotechnology (KGS1092012)
This publication has 48 references indexed in Scilit:
- Non-Motor and Motor Features in LRRK2 Transgenic MicePLOS ONE, 2013
- Genomic responses in mouse models poorly mimic human inflammatory diseasesProceedings of the National Academy of Sciences of the United States of America, 2013
- Progressive degeneration of human neural stem cells caused by pathogenic LRRK2Nature, 2012
- The role of leucine-rich repeat kinase 2 (LRRK2) in Parkinson's diseaseNature Reviews Neuroscience, 2010
- Non‐motor symptoms in Parkinson’s diseaseEuropean Journal of Neurology, 2008
- PET in LRRK2 mutations: comparison to sporadic Parkinson's disease and evidence for presymptomatic compensationBrain, 2005
- Clinical features of LRRK2‐associated Parkinson's disease in central NorwayAnnals of Neurology, 2005
- The prepattern transcription factor Irx2, a target of the FGF8/MAP kinase cascade, is involved in cerebellum formationNature Neuroscience, 2004
- The Iroquois Homeobox Gene Irx2 Is Not Essential for Normal Development of the Heart and Midbrain-Hindbrain Boundary in MiceMolecular and Cellular Biology, 2003
- Initial sequencing and comparative analysis of the mouse genomeNature, 2002