Effect of histone deacetylases in pathogenesis of Alzheimer’s disease

Zhenzhen ZHAO; Guofeng MENG; Weidong ZHANG

doi:10.16306/j.1008-861x.2022.03.001

您当前的位置：

首页 >

文章列表页 >

Effect of histone deacetylases in pathogenesis of Alzheimer’s disease

Scholar Forum | 更新时间：2022-08-29

- Effect of histone deacetylases in pathogenesis of Alzheimer’s disease
- Academic Journal of Shanghai University of Traditional Chinese Medicine Vol. 36, Issue 3, Pages: 1-6(2022)
- 作者机构：
  
  1.上海中医药大学交叉科学研究院（上海　201203）
- 作者简介：
- 基金信息：
- DOI：10.16306/j.1008-861x.2022.03.001
  CLC：
扫描看全文
赵珍珍,孟国锋,张卫东.组蛋白去乙酰化酶在阿尔茨海默病发病机制中的作用[J].上海中医药大学学报,2022,36(03):1-6.

ZHAO Zhenzhen,MENG Guofeng,ZHANG Weidong.Effect of histone deacetylases in pathogenesis of Alzheimer’s disease[J].Academic Journal of Shanghai University of Traditional Chinese Medicine,2022,36(03):1-6.
赵珍珍,孟国锋,张卫东.组蛋白去乙酰化酶在阿尔茨海默病发病机制中的作用[J].上海中医药大学学报,2022,36(03):1-6. DOI： 10.16306/j.1008-861x.2022.03.001.

ZHAO Zhenzhen,MENG Guofeng,ZHANG Weidong.Effect of histone deacetylases in pathogenesis of Alzheimer’s disease[J].Academic Journal of Shanghai University of Traditional Chinese Medicine,2022,36(03):1-6. DOI： 10.16306/j.1008-861x.2022.03.001.

摘要

阿尔茨海默病（AD）作为人体衰老过程中最普遍的神经退行性疾病之一，随着全世界人口老龄化程度加重，发病率不断增长，给患者家庭和社会带来严重健康威胁和经济负担。近年来，大量的研究发现组蛋白乙酰化和去乙酰化作为一种表观遗传修饰在阿尔茨海默病发生过程中起着重要的调控作用。组蛋白去乙酰化酶（HDACs）可以使细胞中组蛋白发生去乙酰化，导致染色质收缩紧密，从而抑制基因转录，调控蛋白质的稳态，影响细胞代谢、衰老、死亡等生命过程。归纳总结HDACs家族在AD发生过程中的作用效应和相关HDACs抑制剂在AD中的研究概况，为了解HDACs家族介导生物调控机制提供新思路，为HDACs抑制剂治疗AD提供重要的理论指导。

Abstract

Alzheimer’s disease（AD） is one of the most common neurodegenerative diseases during human aging. With the increasing aging of the world’s population， the incidence of AD is also increasing， which brings serious health threat and economic burden to patients’ families and society. In recent years， numerous studies have found that histone acetylation and deacetylation， as an epigenetic modification， play an important regulatory role in the pathogenesis of AD. Histone deacetylases （HDACs） can deacetylate histone in cell， leading to chromatin contraction， thereby inhibiting gene transcription， regulating protein homeostasis， affecting cell metabolism， aging， apoptosis and other life processes. The role and function of the HDACs family in the pathogenesis of AD and the research overview of related HDACs inhibitors in AD are summarized to provide new ideas for understanding the biological regulation mechanism mediated by the HDACs family and important theoretical guidance for the treatment of AD with HDACs inhibitors.

关键词

阿尔茨海默病组蛋白去乙酰化组蛋白去乙酰化酶组蛋白去乙酰化酶抑制剂

Keywords

Alzheimer’s diseasehistone deacetylationhistone deacetylasesHDACs inhibitors

references

KUKULL W A，BOWEN J D. Dementia epidemiology［J］. Med Clin North Am， 2002， 86（3）： 573-590.

MATTSON M P. Pathways towards and away from Alzheimer’s disease［J］. Nature， 2004， 430（7000）： 631-639.

DEKOSKY S T，MAREK K. Looking backward to move forward：early detection of neurodegenerative disorders［J］. Science，2003，302（5646）： 830-834.

NGANDU T，LEHTISALO J， SOLOMON A，et al. A 2 year multidomain intervention of diet，exercise，cognitive training，and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people （FINGER）：a randomised controlled trial［J］. Lancet， 2015， 385（9984）： 2255-2263.

COTMAN C W， BERCHTOLD N C. Exercise：a behavioral intervention to enhance brain health and plasticity［J］.Trends Neurosci， 2002， 25（6）： 295-301.

MILLER G. Epigenetics. A role for epigenetics in cognition［J］. Science， 2010， 329（5987）： 27.

BARNES P J. Targeting the epigenome in the treatment of asthma and chronic obstructive pulmonary disease［J］. Proc Am Thorac Soc， 2009， 6（8）： 693-696.

KEENEN B， DELA SERNA I L. Chromatin remodeling in embryonic stem cells： regulating the balance between pluripotency and differentiation［J］. Cell Physiol， 2009， 219（1）： 1-7.

PONS D，DEVRIES F R，VAN DEN ELSEN P G， et al. Epigenetic histone acetylation modifiers in vascular remodelling：new targets for therapy in cardiovascular disease［J］. Eur Heart J， 2009， 30（3）： 266-277.

WITT O， DEUBZER H E， MILDE T，et al. HDAC family：What are the cancer relevant targets？［J］. Cancer Lett， 2009， 277（1）： 8-21.

MIHAYLOVA M M， SHAW R J. Metabolic reprogramming by class Ⅰ and Ⅱ histone deacetylases［J］. Trends Endocrinol Metab， 2003， 24（1）： 48-57.

GRÄFF J， REI D， GUAN J S， et al. An epigenetic blockade of cognitive functions in the neurodegenerating brain［J］. Nature， 2012， 483（7388）： 222-226.

KOUZARIDES T. Chromatin modifications and their function［J］. Cell， 2007， 128（4）： 693-705.

ROTH S Y， DENU J M， ALLIS C D. Histone acetyltransferases［J］. Annu Rev Biochem， 2001， 70： 81-120.

BROWNELL J E， ZHOU J， RANALLI T，et al. Tetrahymena histone acetyltransferase A：a homolog to yeast Gcn5p linking histone acetylation to gene activation［J］. Cell， 1996， 84（6）： 843-851.

LORBECK M， PIROOZNIA K， SARTHI J， et al. Microarray analysis uncovers a role for Tip60 in nervous system function and general metabolism［J］. PLoS One， 2011， 6（4）： e18412.

SARTHI J，ELEFANT F. dTip60 HAT activity controls synaptic bouton expansion at the Drosophila neuromuscular junction［J］. PLoS One， 2011， 6（10）： e26202.

PIROOZNIA S K， SARTHI J，JOHNSON A A， et al. Tip60 HAT activity mediates APP induced lethality and apoptotic cell death in the CNS of a Drosophila Alzheimer’s disease model［J］. PLoS One， 2012， 7（7）： e41776.

BOUSIGES O， VASCONCELOS A P， NEIDL R， et al. Spatial memory consolidation is associated with induction of several lysine-acetyltransferase （histone acetyltransferase） expression levels and H2B/H4 acetylation-dependent transcriptional events in the rat hippocampus［J］. Neuropsychopharmacology， 2010， 35（13）： 2521-2537.

ROUAUX C， JOKIC N， MBEBI C， et al. Critical loss of CBP/P300 histone acetylase activity by caspase-6 during neurodegeneration［J］. EMBO J， 2003， 22（24）： 6537-6549.

WU C W， MILOSLAVSKAYA I， DEMONTIS S， et al. Regulation of cellular response to oncogenic and oxidative stress by Seladin-1［J］. Nature， 2004， 432（7017）： 640-645.

CHAMI L， BUGGIA-PRÉVOT V， DUPLAN E， et al. Nuclear factor-κB regulates βAPP and β- and γ-secretases differently at physiological and supraphysiological Aβ concentrations［J］. J Biol Chem， 2012， 287（29）： 24573-24584.

LIU R G，LEI J X， LUO C， et al. Increased EID1 nuclear translocation impairs synaptic plasticity and memory function associated with pathogenesis of Alzheimer's disease［J］. Neurobiol Dis， 2012， 45（3）： 902-912.

VALOR L M，PULOPULOS M M， JIMENEZ-MINCHAN M，et al. Ablation of CBP in forebrain principal neurons causes modest memory and transcriptional defects and a dramatic reduction of histone acetylation but does not affect cell viability［J］. Neurosci，2011， 31（5）： 1652-1663.

AUBRY S， SHIN W， CRARY J F， et al. Assembly and interrogation of Alzheimer’s disease genetic networks reveal novel regulators of progression［J］. PLoS One， 2015， 10（3）： e0120352.

MARAMBAUD P， WEN P H， DUTT A， et al. A CBP binding transcriptional repressor produced by the PS1/epsilon-cleavage of N-cadherin is inhibited by PS1 FAD mutations［J］. Cell， 2003， 114（5）： 635-645.

LU X，DENG Y S， YU D H， et al. Histone acetyltransferase p300 mediates histone acetylation of PS1 and BACE1 in a cellular model of Alzheimer’s disease［J］. PLoS One， 2014， 9（7）： e103067.

SAURA C A， CHOI S Y， BEGLOPOULOS V， et al. Loss of presenilin function causes impairments of memory and synaptic plasticity followed by age-dependent neurodegeneration［J］. Neuron， 2004， 42（1）： 23-36.

CHUANG D M， LENG Y， MARINOVA Z， et al. Multiple roles of HDAC inhibition in neurodegenerative conditions［J］. Trends Neurosci， 2009， 32（11）： 591-601.

ZHANG Y， NG H H， ERDJUMENT-BROMAGE H， et al. Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation［J］. Genes Dev， 1999， 13（15）： 1924-1935.

BERNSTEIN B E， TONG J K， SCHREIBER S L. Genomewide studies of histone deacetylase function in yeast［J］. Proc Natl Acad Sci U S A， 2000， 97（25）： 13708-13713.

UHLÉN M， FAGERBERG L， HALLSTRÖM B M， et al. Proteomics. Tissue-based map of the human proteome［J］. Science， 2015， 347（6220）： 1260419.

HAGGARTY S J， KOELLER K M， WONG J C， et al. Domain-selective small-molecule inhibitor of histone deacetylase 6 （HDAC6）-mediated tubulin deacetylation［J］. Proc Natl Acad Sci U S A， 2003， 100（8）： 4389-4394.

GOVINDARAJAN N， RAO P，BURKHARDT S， et al. Reducing HDAC6 ameliorates cognitive deficits in a mouse model for Alzheimer’s disease［J］. EMBO Mol Med， 2013， 5（1）： 52-63.

Views

332

下载量

CSCD

CNKI被引量

Alert me when the article has been cited

提交

Tools

Publicity Resources

Exploring common material basis and mechanism of volatile oil from Acori Tatarinowii Rhizoma in intervening central nervous system diseases based on network pharmacology

Effects of Daimengkai Granule on mitochondrial kinetics in brain tissue of Alzheimer’s disease mice

Effect of Music Electro-acupuncture on Learning and Memory Behavior and Aβ1-42Level in Hippocampal CA3 Region in AD Model Mice

Inhibitory effects of active extracts and effective compounds of Chinese herbal medicines on enzymatic and non-enzymatic functions of butyrylcholinesterase in Alzheimer’s disease

Research Advances in mechanisms of Rehmanniae Radix Praeparata and Acori Tatarinowii Rhizoma in prevention and treatment of Alzheimer’s disease

Related Author

No data

Related Institution

MOE Key Laboratory for Standardization of Chinese Medicines， Institute of Chinese Materia Medica， Shanghai University of Traditional Chinese Medicine

Shanghai R&D Centre for Standardization of Chinese Medicines

Shanghai Geriatric Institute of Chinese Medicine

WANG Xin,HAN Xiang-bo,PARK CHAN HUNSONG Meng School of Acupuncture-moxibustion and Tuina of Beijing University of Traditional Chinese Medicine

Center for Disease Control and Prevention,Pingchuan District

⁰