学术报告

Epigenetic control of higher order brain function in Alzheimer’s disease

发布时间:2018-04-17  

报告人:Felice Elefant,PhD

Associate Professor, Co-Director of the Biology Graduate Program

Department of Biology, Drexel University, Philadelphia, USA

主持人:祝献民 副研究员

时 间:2018417日 周二上午10:00-11:30
地 点:医学楼1102

Dr. Elefant’s lab focused on understanding the mechanisms that govern epigenetic regulation of higher order brain function. Epigenetic gene control in the brain is a fundamental mechanism for orchestrating dynamic gene expression profiles critical for cognitive function. One of the best characterized epigenetic marks crucial for learning and memory is histone acetylation that regulates cognitive gene expression by controlling chromatin packaging in neurons. Histone acetylation is regulated by the antagonistic activities of histone acetyltransferases (HATs) and histone deacetylases (HDACs). Impairment of epigenetic gene control mechanisms in the brain involving reduced histone acetylation levels causes significant cognitive deficits that are a debilitating hallmark of most neurodegenerative disorders, including Alzheimer’s disease (AD). Unfortunately, little is known about the select HATs that modify the neural epigenome, and the corresponding gene expression programs they control.

Recently, her lab made the exciting discovery that Tip60 HAT action is critical for cognitive processes via its role in epigenetic neural gene control and remarkably, plays a neuroprotective role under in vivo disease state AD neurodegenerative conditions. They are currently exploring the mechanisms underlying neural Tip60 HAT function in neuroprotective epigenetic gene control and the beneficial impact that environmental enrichment conditions has on these processes. Their studies should provide new understanding into epigenetic based mechanisms underlying neurodegenerative disorders, and broad insights into synergistic behavioral and HAT based therapeutic approaches for treatment of cognitive disorders.

Selected publications:

  1. Gulchina, Y et al. 2017 Epigenetic mechanisms of synaptic NMDA receptor hypofunction during development of the prefrontal cortex of the MAM model for schizophrenia. J Neurochemistry. 2017. Editorially featured as issue highlight.
  2. Xu S, et al. 2014. Epigenetic control of learning and memory in Drosophila by Tip60 HAT action. Genetics 198(4):1571-86. Editorially featured on cover as Issue Highlight.
  3. Johnson, A, et al. 2013. Increasing Tip60 HAT levels rescues axonal defects and associated behavioral defects in a Drosophila Alzheimer’s disease model. Journal of Neuroscience. Apr 24; 33(17):7535-47.

Featured as a ‘Key Research Article’ in “Psychology Progress”.

  1. Zhu, X et al. 2007. The cloning and characterization of the histone acetyltransferase human homolog Dmel/TIP60 in Drosophila melanogaster: Dmel/TIP60 is essential for multicellular development. Genetics 175, 1229-40.

 

Editorially featured as Issue Highlight.

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