We previously demonstrated that the midnolin gene (MIDN) is a risk factor for Parkinson's disease (PD) in Yamagata and British cohorts, and that neurite outgrowth is abolished by MIDN knockout in PC12 cells. Therefore, drugs that upregulate MIDN may have neurotrophic effects. In this study, acetylcholine increased MIDN promoter activity and gene expression in a concentration-dependent manner in SH-SY5Y cells. These effects were suppressed by atropine and a G inhibitor, YM254890, indicating that muscarinic receptor/G signaling is required for the induction of MIDN by acetylcholine. Our findings suggest that drugs that upregulate MIDN may have therapeutic potential for PD.
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http://dx.doi.org/10.1016/j.jphs.2025.02.006 | DOI Listing |
J Pharmacol Sci
April 2025
Department of Pharmacology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan. Electronic address:
We previously demonstrated that the midnolin gene (MIDN) is a risk factor for Parkinson's disease (PD) in Yamagata and British cohorts, and that neurite outgrowth is abolished by MIDN knockout in PC12 cells. Therefore, drugs that upregulate MIDN may have neurotrophic effects. In this study, acetylcholine increased MIDN promoter activity and gene expression in a concentration-dependent manner in SH-SY5Y cells.
View Article and Find Full Text PDFJ Inflamm Res
February 2025
Department of Pancreatic and Gastric Surgery, Cancer Hospital Chinese Academy of Medical Sciences, Beijing, People's Republic of China.
Background: Pancreatic cancer has one of the worst prognoses of any malignant tumor. The value of MIDN, midnolin-related genes and midnolin-related immune infiltrating cells (MICs) in the prognosis of pancreatic cancer remains unknown.
Methods: Single-cell analysis were used to identify midnolin-related genes.
Biomedicines
January 2025
Medical School, Kunming University of Science and Technology, Kunming 650500, China.
: MIDN (midnolin) is newly discovered method for critically regulating a ubiquitin-independent proteasomal degradation pathway. This study aims to examine the expression, prognostic value, genomic changes, interacting proteins, methylation status, and correlations with the tumor immune microenvironment of MIDN in various cancers. : The GTEx, Depmap, GEPIA2, and Kaplan-Meier Plotter databases are applied to evaluate the MIDN level in tumor and normal tissues and the MIDN prognostic value in cancers.
View Article and Find Full Text PDFMol Cell Biol
October 2024
Department of Pharmacology, Yamagata University School of Medicine, Yamagata, Japan.
Parkinson's disease (PD) is an age-related progressive neurodegenerative disease. Previously, we identified midnolin () as a genetic risk factor for PD. Although copy number loss increases the risk of PD, the molecular function of MIDN remains unclear.
View Article and Find Full Text PDFJ Exp Med
June 2024
Center for the Genetics of Host Defense, University of Texas Southwestern Medical Center, Dallas, TX, USA.
In a genetic screen, we identified two viable missense alleles of the essential gene Midnolin (Midn) that were associated with reductions in peripheral B cells. Causation was confirmed in mice with targeted deletion of four of six MIDN protein isoforms. MIDN was expressed predominantly in lymphocytes where it augmented proteasome activity.
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