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Literature DB >> 23200855

The sirtuin 2 inhibitor AK-7 is neuroprotective in Huntington's disease mouse models.

Vanita Chopra¹, Luisa Quinti, Jinho Kim, Lorraine Vollor, K Lakshmi Narayanan, Christina Edgerly, Patricia M Cipicchio, Molly A Lauver, Soo Hyuk Choi, Richard B Silverman, Robert J Ferrante, Steven Hersch, Aleksey G Kazantsev.

Abstract

Inhibition of sirtuin 2 (SIRT2) deacetylase mediates protective effects in cell and invertebrate models of Parkinson's disease and Huntington's disease (HD). Here we report the in vivo efficacy of a brain-permeable SIRT2 inhibitor in two genetic mouse models of HD. Compound treatment resulted in improved motor function, extended survival, and reduced brain atrophy and is associated with marked reduction of aggregated mutant huntingtin, a hallmark of HD pathology. Our results provide preclinical validation of SIRT2 inhibition as a potential therapeutic target for HD and support the further development of SIRT2 inhibitors for testing in humans.

Entities: Chemical Disease Gene Species

Mesh：

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Year: 2012 PMID： 23200855 PMCID： PMC3534897 DOI： 10.1016/j.celrep.2012.11.001

Source DB: PubMed Journal: Cell Rep Impact factor: 9.423

25 in total

1. SIRT2 inhibition achieves neuroprotection by decreasing sterol biosynthesis.

Authors: Ruth Luthi-Carter; David M Taylor; Judit Pallos; Emmanuel Lambert; Allison Amore; Alex Parker; Hilary Moffitt; Donna L Smith; Heike Runne; Ozgun Gokce; Alexandre Kuhn; Zhongmin Xiang; Michele M Maxwell; Steven A Reeves; Gillian P Bates; Christian Neri; Leslie M Thompson; J Lawrence Marsh; Aleksey G Kazantsev
Journal: Proc Natl Acad Sci U S A Date: 2010-04-08 Impact factor: 11.205

2. Histone deacetylase (HDAC) inhibitors targeting HDAC3 and HDAC1 ameliorate polyglutamine-elicited phenotypes in model systems of Huntington's disease.

Authors: Haiqun Jia; Judit Pallos; Vincent Jacques; Alice Lau; Bin Tang; Andrew Cooper; Adeela Syed; Judith Purcell; Yi Chen; Shefali Sharma; Gavin R Sangrey; Shayna B Darnell; Heather Plasterer; Ghazaleh Sadri-Vakili; Joel M Gottesfeld; Leslie M Thompson; James R Rusche; J Lawrence Marsh; Elizabeth A Thomas
Journal: Neurobiol Dis Date: 2012-05 Impact factor: 5.996

3. SirT2 is a histone deacetylase with preference for histone H4 Lys 16 during mitosis.

Authors: Alejandro Vaquero; Michael B Scher; Dong Hoon Lee; Ann Sutton; Hwei-Ling Cheng; Frederick W Alt; Lourdes Serrano; Rolf Sternglanz; Danny Reinberg
Journal: Genes Dev Date: 2006-04-28 Impact factor: 11.361

4. Cerebral cortex and the clinical expression of Huntington's disease: complexity and heterogeneity.

Authors: H Diana Rosas; David H Salat; Stephanie Y Lee; Alexandra K Zaleta; Vasanth Pappu; Bruce Fischl; Doug Greve; Nathanael Hevelone; Steven M Hersch
Journal: Brain Date: 2008-03-12 Impact factor: 13.501

5. The Sirtuin 2 microtubule deacetylase is an abundant neuronal protein that accumulates in the aging CNS.

Authors: Michele M Maxwell; Elizabeth M Tomkinson; Johnathan Nobles; John W Wizeman; Allison M Amore; Luisa Quinti; Vanita Chopra; Steven M Hersch; Aleksey G Kazantsev
Journal: Hum Mol Genet Date: 2011-07-26 Impact factor: 6.150

6. Chronology of behavioral symptoms and neuropathological sequela in R6/2 Huntington's disease transgenic mice.

Authors: Edward C Stack; James K Kubilus; Karen Smith; Kerry Cormier; Steven J Del Signore; Emmanuel Guelin; Hoon Ryu; Steven M Hersch; Robert J Ferrante
Journal: J Comp Neurol Date: 2005-10-03 Impact factor: 3.215

7. Inhibition of specific HDACs and sirtuins suppresses pathogenesis in a Drosophila model of Huntington's disease.

Authors: Judit Pallos; Laszlo Bodai; Tamas Lukacsovich; Judith M Purcell; Joan S Steffan; Leslie Michels Thompson; J Lawrence Marsh
Journal: Hum Mol Genet Date: 2008-09-01 Impact factor: 6.150

8. Time course of early motor and neuropathological anomalies in a knock-in mouse model of Huntington's disease with 140 CAG repeats.

Authors: Liliana B Menalled; Jessica D Sison; Ioannis Dragatsis; Scott Zeitlin; Marie-Françoise Chesselet
Journal: J Comp Neurol Date: 2003-10-06 Impact factor: 3.215

Review 9. Appearances can be deceiving: phenotypes of knockout mice.

Authors: Ivana Barbaric; Gaynor Miller; T Neil Dear
Journal: Brief Funct Genomic Proteomic Date: 2007-06-20

10. Genetic knock-down of HDAC3 does not modify disease-related phenotypes in a mouse model of Huntington's disease.

Authors: Lara Moumné; Ken Campbell; David Howland; Yingbin Ouyang; Gillian P Bates
Journal: PLoS One Date: 2012-02-08 Impact factor: 3.240

75 in total

1. Cell and Context-Dependent Effects of the Heat Shock Protein DNAJB6 on Neuronal Survival.

Authors: Chad Smith; Santosh R D'Mello
Journal: Mol Neurobiol Date: 2015-10-17 Impact factor: 5.590

2. SIRT2 Plays Significant Roles in Lipopolysaccharides-Induced Neuroinflammation and Brain Injury in Mice.

Authors: Ban Wang; Youjun Zhang; Wei Cao; Xunbing Wei; James Chen; Weihai Ying
Journal: Neurochem Res Date: 2016-06-27 Impact factor: 3.996

3. SIRT2 Inhibition Confers Neuroprotection by Downregulation of FOXO3a and MAPK Signaling Pathways in Ischemic Stroke.

Authors: David T She; Lap Jack Wong; Sang-Ha Baik; Thiruma V Arumugam
Journal: Mol Neurobiol Date: 2018-04-14 Impact factor: 5.590

4. Halistanol sulfates I and J, new SIRT1-3 inhibitory steroid sulfates from a marine sponge of the genus Halichondria.

Authors: Fumiaki Nakamura; Norio Kudo; Yuki Tomachi; Akiko Nakata; Misao Takemoto; Akihiro Ito; Hodaka Tabei; Daisuke Arai; Nicole de Voogd; Minoru Yoshida; Yoichi Nakao; Nobuhiro Fusetani
Journal: J Antibiot (Tokyo) Date: 2017-11-29 Impact factor: 2.649