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Genes critical for development and differentiation of dopaminergic neurons are downregulated in Parkinson's disease.
- Source :
-
Journal of neural transmission (Vienna, Austria : 1996) [J Neural Transm (Vienna)] 2023 Apr; Vol. 130 (4), pp. 495-512. Date of Electronic Publication: 2023 Feb 23. - Publication Year :
- 2023
-
Abstract
- We performed transcriptome analysis using RNA sequencing on substantia nigra pars compacta (SNpc) from mice after acute and chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment and from Parkinson's disease (PD) patients. Acute and chronic exposure to MPTP resulted in decreased expression of genes involved in sodium channel regulation. However, upregulation of pro-inflammatory pathways was seen after single dose but not after chronic MPTP treatment. Dopamine biosynthesis and synaptic vesicle recycling pathways were downregulated in PD patients and after chronic MPTP treatment in mice. Genes essential for midbrain development and determination of dopaminergic phenotype such as, LMX1B, FOXA1, RSPO2, KLHL1, EBF3, PITX3, RGS4, ALDH1A1, RET, FOXA2, EN1, DLK1, GFRA1, LMX1A, NR4A2, GAP43, SNCA, PBX1, and GRB10 were downregulated in human PD and overexpression of GFP tagged LMX1B rescued MPP <superscript>+</superscript> induced death in SH-SY5Y neurons. Downregulation of gene ensemble involved in development and differentiation of dopaminergic neurons indicate their potential involvement in pathogenesis and progression of human PD.<br /> (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)
Details
- Language :
- English
- ISSN :
- 1435-1463
- Volume :
- 130
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of neural transmission (Vienna, Austria : 1996)
- Publication Type :
- Academic Journal
- Accession number :
- 36820885
- Full Text :
- https://doi.org/10.1007/s00702-023-02604-x