title: The role of myocardin-related transcription factor-A in Aβ25-35 induced neuron apoptosis and synapse injury.
abstract: Myocardin-related transcription factor-A (MRTF-A) highly expressed in brain has been demonstrated to promote neuronal survival via regulating the transcription of related target genes as a powerful co-activator of serum response factor (SRF). However, the role of MRTF-A in Alzheimer's disease (AD) is still unclear. Here, we showed that MRTF-A was significantly downregulated in cortex of the Aβ25-35-induced AD rats, which played a key role in Aβ25-35 induced cerebral neuronal degeneration in vitro. Bilateral intracerebroventricular injection of Aβ25-35 caused significantly MRTF-A expression decline in cortex of rats, along with significant neuron apoptosis and plasticity damage. In vitro, transfection of MRTF-A into primary cultured cortical neurons prevented Aβ25-35 induced neuronal apoptosis and synapses injury. And luciferase reporter assay determined that MRTF-A could bind to and enhance the transactivity of the Mcl-1 (Myeloid cell leukemia-1) and Arc (activity-regulated cytoskeletal-associated protein) promoters by activating the key CArG box element. These data demonstrated that the decreasing of endogenous MRTF-A expression might contribute to the development of AD, whereas the upregulation MRTF-A in neurons could effectively reduce Aβ25-35 induced synapse injury and cell apoptosis. And the underlying mechanism might be partially due to MRTF-A-mediated the transcription and expression of Mcl-1 and Arc by triggering the CArG box.
authors.affiliation: Department of Pharmacology, Medical College of Wuhan University of Science and Technology, Wuhan 430080, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Tianyou Hospital Affiliated to Wuhan University of Science and Technology, Wuhan 430064, PR China.
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Pan
authors.affiliation: Department of Pharmacology, Medical College of Wuhan University of Science and Technology, Wuhan 430080, PR China. Electronic address: huxiamin@wust.edu.cn.
authors.forename: Xia-Min
authors.initials: XM
authors.lastname: Hu
authors.affiliation: Department of Pharmacology, Medical College of Wuhan University of Science and Technology, Wuhan 430080, PR China.
authors.forename: Xiao-Lu
authors.initials: XL
authors.lastname: Cao
authors.affiliation: Department of Pharmacology, Medical College of Wuhan University of Science and Technology, Wuhan 430080, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Medical College of Wuhan University of Science and Technology, Wuhan 430080, PR China.
authors.forename: Zhen-Li
authors.initials: ZL
authors.lastname: Min
authors.affiliation: Department of Pharmacology, Medical College of Wuhan University of Science and Technology, Wuhan 430080, PR China.
authors.forename: Shi-Qiang
authors.initials: SQ
authors.lastname: Xu
authors.affiliation: Department of Pharmacology, Medical College of Wuhan University of Science and Technology, Wuhan 430080, PR China.
authors.forename: Wan
authors.initials: W
authors.lastname: Xiao
authors.affiliation: Department of Pharmacology, Medical College of Wuhan University of Science and Technology, Wuhan 430080, PR China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Yuan
authors.affiliation: Department of Pharmacology, Medical College of Wuhan University of Science and Technology, Wuhan 430080, PR China.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Medical College of Wuhan University of Science and Technology, Wuhan 430080, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Department of Pharmacology, Medical College of Wuhan University of Science and Technology, Wuhan 430080, PR China.
authors.forename: Shu-Qi
authors.initials: SQ
authors.lastname: Zhao
authors.affiliation: Department of Pharmacology, Medical College of Wuhan University of Science and Technology, Wuhan 430080, PR China.
authors.forename: Xing
authors.initials: X
authors.lastname: Hong
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002470:Cell Survival; D002540:Cerebral Cortex / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation; D008297:Male; D009410:Nerve Degeneration / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D009687:Nuclear Proteins; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D051381:Rats; D017207:Rats, Sprague-Dawley; D026362:Serum Response Factor / Q000378:metabolism; D013569:Synapses / Q000502:physiology; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D015854:Up-Regulation; D000099251:Myocardin
chemical_list: D016229:Amyloid beta-Peptides; D009687:Nuclear Proteins; D010446:Peptide Fragments; D026362:Serum Response Factor; D015534:Trans-Activators; D014157:Transcription Factors; D000099251:Myocardin; C074636:amyloid beta-protein (25-35); C557977:myocardin-related transcription factor-A, rat
keywords: Alzheimer; Apoptosis; Arc; MRTF-A; Mcl-1; Synaptic injury