CAJ | 학술논문

该文首先对什么是表观遗传学及其细胞学基础作了介绍,随后,对认知功能中的表观遗传学机制的研究进展进行了综述。各方面研究一致证明,在海马、皮层及其它脑区发生的表观遗传学改变如组蛋白的乙酰化、甲基化、磷酸化、泛素化、多聚( ADP-核糖)聚合酶化和DNA甲基化可稳定地改变动物的行为,包括学习、记忆、突触可塑性、抑郁、药物成瘾等。不过,在长记忆和突触可塑形成过程中,需要CREB结合蛋白CP的存在并与CREB相结合,最后导致与记忆及突触可塑性有关的基因(如Zif/268,Greb,Bdnf,Reelin等)的转录和表达。相反,在衰老和神经退行性疾病脑内出现表观遗传学的异常改变,如组蛋白低甲基化、组蛋白去乙酰化转移酶活性增加等。鉴于上述,对神经退行性疾病的治疗策略是：提高组蛋白乙酰化和组蛋白、DNA甲基化,应用 HDAC抑制剂及RNA干扰( RNAi)可有效地改善记忆,提高突触可塑性和阻遏学习记忆下降。
해문수선대십요시표관유전학급기세포학기출작료개소,수후,대인지공능중적표관유전학궤제적연구진전진행료종술。각방면연구일치증명,재해마、피층급기타뇌구발생적표관유전학개변여조단백적을선화、갑기화、린산화、범소화、다취( ADP-핵당)취합매화화DNA갑기화가은정지개변동물적행위,포괄학습、기억、돌촉가소성、억욱、약물성은등。불과,재장기억화돌촉가소형성과정중,수요CREB결합단백CP적존재병여CREB상결합,최후도치여기억급돌촉가소성유관적기인(여Zif/268,Greb,Bdnf,Reelin등)적전록화표체。상반,재쇠로화신경퇴행성질병뇌내출현표관유전학적이상개변,여조단백저갑기화、조단백거을선화전이매활성증가등。감우상술,대신경퇴행성질병적치료책략시：제고조단백을선화화조단백、DNA갑기화,응용 HDAC억제제급RNA간우( RNAi)가유효지개선기억,제고돌촉가소성화조알학습기억하강。
The definition of epigenetics and its cellular basis are introduced firstly in the paper. Then, the research progress on the relationship between cognition and epigenetic changes is re-viewed in detail. In conclusion, epigenetic modifications occur-ring in hippocampus, cortex and other brain areas such as methy-lation , phosphorylation , ubiquitination , poly ( ADP-ribos ) poly-merases and DNA methylation may certainly change animal be-haviors including learning, memory, synaptic plasticity, depres-sion, drug abuse and so on. Long-term memory and long-term potentiation( LTP) , activation of AMPK-ERK signal transduction path-way and activation of key gene regulated by CREB-ABP transcriptional complex as well as transcription and expression of memory and synaptic plasticity related genes ( Zif/268, Creb, Bdnf, reelin ) are required. In contrast, epigenetic abnormal changes such as histone and DNA hypomethylation and increase of HDAC activity are observed in brains of aging and neurodegen-erative diseases. Therefore, the main epigenetic treatments for cognitive impairments are increasing histone and DNA methyla-tion, using HDAC inhibitors and RNA interference ( RNAi) to promote formation of long term memory and long term potentia-tion, block learning and memory decline.