Midnolin gene expression is enhanced by Gq-coupled muscarinic acetylcholine receptor stimulation in SH-SY5Y human neuroblastoma cells

  • J Pharmacol Sci. 2025 Apr;157(4):229-232. doi: 10.1016/j.jphs.2025.02.006.
Ikuo Norota  1 ,  Yusuke Zuiki  1 ,  Ayano Chiba  1 ,  Mikako Nagashima  1 ,  Jiro Ogura  2 ,  Hiroaki Yamaguchi  2 ,  Kuniaki Ishii  1 ,  Yutaro Obara  3
Affiliations
  • 1. Department of Pharmacology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan.
  • 2. Department of Pharmaceutical Sciences, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan.
  • 3. Department of Pharmacology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan. Electronic address: [email protected].
PMID: 40058942 DOI: 10.1016/j.jphs.2025.02.006
Abstract

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 Gq inhibitor, YM254890, indicating that muscarinic receptor/Gq signaling is required for the induction of MIDN by acetylcholine. Our findings suggest that drugs that upregulate MIDN may have therapeutic potential for PD.

Keywords
Acetylcholine (ACh); Midnolin (MIDN); Parkinson's disease (PD).
Products