Activation of Transcription Factor MEF2D by Bis(3)-cognitin Protects Dopaminergic Neurons and Ameliorates Parkinsonian Motor Defects

• Type of Material: Article
• Authors: Lu Yao, Emory University; Wenming Li, Emory University; Hua She, Emory University; Juan Dou, Emory University; Leili Jia, Emory University; Yingli He, Emory University; Qian Yang, Emory University; Jinqiu Zhu, Emory University; Natalie L. Capiro, Tufts University; Douglas Walker, Tufts University; Kurt D. Pennell, Tufts University; Yuanping Pang, Mayo Foundation for Medical Education and Research; Yong Liu, Xi'an Jiaotong University College of Medicine; Yifan Han, Hong Kong Polytechnic University; Zixu Mao, Emory University
• Language: English
• Date: 2012-10-05
• Publisher: American Society for Biochemistry and Molecular Biology
• Publication Version: Final Published Version
• Copyright Statement: © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.
• Final Published Version (URL): http://www.jbc.org/content/287/41/34246
• Title of Journal or Parent Work: Journal of Biological Chemistry
• ISSN: 0021-9258
• Volume: 287
• Issue: 41
• Start Page: 34246
• End Page: 34255
• Grant/Funding Information: This work was supported in part by National Institutes of Health Grants AG023695 and NS048254 (to Z. M.), 1P50NS071669 (to W. L.), and ES015317 and ES015317-002 (to Z. M.).; This work was also supported in part by a grant from the Michael J. Fox Foundation (to Z. M.), in part by grants from the Research Grants Council of Hong Kong (5609/09M; 5610/11M) and the Hong Kong Polytechnic University (G-U952) (to Y. H.), and in part by National Science Foundation Grant CHE-03200783 (to K. D. P.).
• Keywords: Transcription Factors; Neuroprotection; Mitochondria; Parkinson Disease; Neurobiology; MEF2D
• Research Categories: Biology, Neuroscience; Health Sciences, Pharmacology

Abstract

Background: Dysregulation of myocyte enhancer factor 2D (MEF2D) is implicated in the pathogenic process of Parkinson disease (PD). Results: A small molecule bis(3)-cognitin activates MEF2D and protects Parkinsonian impairments. Conclusion: Bis(3)-cognitin provides protection of dopaminergic neurons in a model of PD by reversing MEF2D dysfunction. Significance: Activation of MEF2D by pharmacological approach has the potential to be a novel therapeutic for PD.