n epigenetic blockade of cognitive functions in the neurodegenerating brain (Nature, 2012, 483:222-226)

報告日期: 2012/12/07
報告時間: 15:10/16:00
報告學生: 劉郁芝
講評老師: 許桂森
附件下載: 下載[1250-1349149987-1.pdf] 

An epigeneticblockade of cognitive functions in the neurodegenerating brain

Johannes Graff, Damien Rei, Ji-Song Guan, Wen-YuanWang, Jinsoo Seo, Krista M. Hennig,Thomas J. F. Nieland, Daniel M. Fass, Patricia F. Kao, Martin Kahn, Susan C. Su, Alireza Samiei, Nadine Joseph,Stephen J. Haggarty, Ivana Delalle & Li-Huei Tsai

Nature 483,222–226(2012)

Speaker: Yu-Chih Liu                                                     Time: 2012.12.07

                               Commentator:Kuei-Sen Hsu Ph.D.                                Place: class 602


Neurodegenerative disease is recognized as a range of diseases which primarily affect the structure, function of neurons in the human brain. In most neurodegenerative diseases of central nervous system, cognitive decline is a common symptom. However, the underlying mechanism of such impairment remains unknown. Epigenetic modulation has been implicated to have the pivotal role in diseases progression, including neurodegenerative disease. Moreover, learning and memory formation require stable gene expression. Therefore, the epigenetic regulators may be the mediator in the pathological linkage between neurodegeneration and cognitive decline. Histone deacetylase 2 (HDAC2) is one of the epigenetic regulator, which has been reported as a negative regulator in memory formation and synaptic plasticity. In this article, authors proposed that HDAC2 is the regulator modulated the cognitive functions in the neurodegenerative disease. They found that the mRNA and protein level of HDAC2 is elevated in the neurodegenerative model. Moreover, mRNA expression levels of the memory formation and synaptic plasticity associated genes, which were regulated by HDAC2, were decreased. On the contrary, reducing HDAC2 levels in neurodegenerative mouse model alleviates memory deficits. Furthermore, they uncover the underlying mechanism of HDAC2 up-regulation. To confirm their finding, they checked the protein level of HDAC2 in human post-mortem samples and found that HDAC2 is up-regulated in early stage of Alzheimer’s disease. These results demonstrated that HDAC2-mediated epigenetic blockade of neuroplasticity-related gene expression could lead to cognitive deficits in neurodegerative disease, especially Alzheimer’s disease. Therefore, HDAC2 may be the potential therapeutic target of Alzheimer’s disease. HDAC2 inhibition probably reinstates transcriptional, morphological and synaptic plasticity in surviving neurons of the neurodegenerating brain.


1.     Guan, J.S., et al. HDAC2 negatively regulates memory formation and synaptic plasticity. Nature 459, 55-60 (2009).