Inhibition of Histone Acetylation by ANP32A Induces Memory Deficits
Inhibition of Histone Acetylation by ANP32A Induces Memory Deficits
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ANP32A 抑制组蛋白乙酰化会导致记忆缺陷
DOI：
10.3233/jad-180090
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发表时间：
2018-01-01
影响因子：
4
通讯作者：
Li, Gong-Ping
中科院分区：
文献类型：
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作者：
Chai, Gao-Shang;Feng, Qiong;Li, Gong-Ping
越来越多的证据表明，组蛋白乙酰化水平降低与正常衰老和神经退行性疾病有关。最近，我们发现ANP32A，INHAT（乙酰转移酶抑制剂），抑制组蛋白乙酰化的关键组成部分，在老年和认知受损的C57小鼠和表达野生型人全长tau（htau）转基因小鼠增加。下调ANP32A通过增加组蛋白乙酰化上调突触相关蛋白的表达来恢复认知功能和突触可塑性。然而，没有直接证据表明ANP32A可以诱导神经变性和记忆缺陷。在本研究中，我们在C57小鼠海马CA3区过表达ANP32A，发现ANP32A过表达诱导认知能力和突触可塑性缺陷，突触相关蛋白表达和组蛋白乙酰化降低。结合我们最近的研究，我们的研究结果表明，上调ANP32A诱导的抑制组蛋白乙酰化可能是神经退行性疾病认知功能下降的基础，抑制ANP32A可能代表了一种有前途的治疗方法，包括阿尔茨海默病在内的神经退行性疾病。
There is accumulating evidence that decreased histone acetylation is involved in normal aging and neurodegenerative diseases. Recently, we found that ANP32A, a key component of INHAT (inhibitor of acetyltransferases) that suppresses histone acetylation, increased in aged and cognitively impaired C57 mice and expressing wild-type human full length tau (htau) transgenic mice. Downregulating ANP32A restored cognitive function and synaptic plasticity through upregulation of the expressions of synaptic-related proteins via increasing histone acetylation. However, there is no direct evidence that ANP32A can induce neurodegeneration and memory deficits. In the present study, we overexpressed ANP32A in the hippocampal CA3 region of C57 mice and found that ANP32A overexpression induced cognitive abilities and synaptic plasticity deficits, with decreased synaptic-related protein expression and histone acetylation. Combined with our recent studies, our findings reveal that upregulated ANP32A induced-suppressing histone acetylation may underlie the cognitive decline in neurodegenerative disease, and suppression of ANP32A may represent a promising therapeutic approach for neurodegenerative diseases including Alzheimer's disease.