Disruption of Tip60 HAT mediated neural histone acetylation homeostasis is an early common event in neurodegenerative diseases.
Disruption of Tip60 HAT mediated neural histone acetylation homeostasis is an early common event in neurodegenerative diseases.
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TIP60 HAT介导的神经组蛋白乙酰化稳态的破坏是神经退行性疾病的早期常见事件。
DOI：
10.1038/s41598-020-75035-3
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发表时间：
2020-10-26
影响因子：
4.6
通讯作者：
Elefant F
中科院分区：
文献类型：
--
作者：
Beaver M;Bhatnagar A;Panikker P;Zhang H;Snook R;Parmar V;Vijayakumar G;Betini N;Akhter S;Elefant F
Epigenetic dysregulation is a common mechanism shared by molecularly and clinically heterogenous neurodegenerative diseases (NDs). Histone acetylation homeostasis, maintained by the antagonistic activity of histone acetyltransferases (HATs) and histone deacetylases (HDACs), is necessary for appropriate gene expression and neuronal function. Disruption of neural acetylation homeostasis has been implicated in multiple types of NDs including Alzheimer’s disease (AD), yet mechanisms underlying alterations remain unclear. We show that like AD, disruption of Tip60 HAT/HDAC2 balance with concomitant epigenetic repression of common Tip60 target neuroplasticity genes occurs early in multiple types of Drosophila ND models such as Parkinson’s Disease (PD), Huntington’s Disease (HD) and Amyotrophic Lateral Sclerosis (ALS). Repressed neuroplasticity genes show reduced enrichment of Tip60 and epigentic acetylation signatures at all gene loci examined with certain genes showing inappropriate HDAC2 repressor enrichment. Functional neuronal consequences for these disease conditions are reminiscent of human pathology and include locomotion, synapse morphology, and short-term memory deficits. Increasing Tip60 HAT levels specifically in the mushroom body learning and memory center in the Drosophila brain protects against locomotion and short-term memory function deficits in multiple NDs. Together, our results support a model by which Tip60 protects against neurological impairments in different NDs via similar modes of action.
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DOI：
10.1073/pnas.1012851108
发表时间：
2010-12-28
影响因子：
11.1
作者：
Caccamo, Antonella;Maldonado, Monica A.;Oddo, Salvatore
通讯作者：
Oddo, Salvatore
DOI：
10.1097/nen.0b013e3181ddd404
发表时间：
2010-06-01
影响因子：
3.2
作者：
Janssen, Claas;Schmalbach, Sonja;Petri, Susanne
通讯作者：
Petri, Susanne
影响因子：
4.6
作者：
Barham C;Fil D;Byrum SD;Rahmatallah Y;Glazko G;Kiaei M
通讯作者：
Kiaei M
影响因子：
15.9
作者：
Chuang, De-Maw;Leng, Yan;Marinova, Zoya;Kim, Hyeon-Ju;Chiu, Chi-Tso
通讯作者：
Chiu, Chi-Tso
影响因子：
5.3
作者：
Didonna, Alessandro;Opal, Puneet
通讯作者：
Opal, Puneet