共查询到20条相似文献,搜索用时 8 毫秒
1.
2.
3.
4.
5.
6.
Kaichi Yoshizaki Ryuichi Kimura Hisato Kobayashi Shinya Oki Takako Kikkawa Lingling Mai Kohei Koike Kentaro Mochizuki Hitoshi Inada Yasuhisa Matsui Tomohiro Kono Noriko Osumi 《EMBO reports》2021,22(2)
Advanced paternal age can have deleterious effects on various traits in the next generation. Here, we establish a paternal‐aging model in mice to understand the molecular mechanisms of transgenerational epigenetics. Whole‐genome target DNA methylome analyses of sperm from aged mice reveal more hypo‐methylated genomic regions enriched in REST/NRSF binding motifs. Gene set enrichment analyses also reveal the upregulation of REST/NRSF target genes in the forebrain of embryos from aged fathers. Offspring derived from young mice administrated with a DNA de‐methylation drug phenocopy the abnormal vocal communication of pups derived from aged fathers. In conclusion, hypo‐methylation of sperm DNA can be a key molecular feature modulating neurodevelopmental programs in offspring by causing fluctuations in the expression of REST/NRSF target genes. 相似文献
7.
Stepwise assembly of functional C‐terminal REST/NRSF transcriptional repressor complexes as a drug target 下载免费PDF全文
Ken Inui Zongpei Zhao Juan Yuan Sakthidasan Jayaprakash Le T. M. Le Srdja Drakulic Bjoern Sander Monika M. Golas 《Protein science : a publication of the Protein Society》2017,26(5):997-1011
8.
9.
NRSE 与 NRSF 及其对神经元特异性基因表达的调控作用 总被引:3,自引:0,他引:3
神经限制性沉默元件 (NRSE) 是一段长度为 21~23 bp 的保守 DNA 序列,存在于许多神经元特异表达基因的转录调控区中,神经限制性沉默因子 (NRSF) 能特异性结合到 NRSE dsDNA 上,并通过其 N 端和 C 端阻遏结构域分别连接共阻遏蛋白 Sin3A/B 和 CoREST , Sin3A 招募 HDAC 对组蛋白进行去乙酰基化修饰, CoREST 则作为平台蛋白招募特异的“沉默组件”,以此维持基因沉默 . 最近的研究显示, NRSE dsRNA 能在转录水平与 NRSF 蛋白直接作用,而不是作为 siRNA 或 miRNA 在转录后水平启动神经元特异性基因的表达 . 相似文献
10.
11.
van Loo KM Schaub C Pernhorst K Yaari Y Beck H Schoch S Becker AJ 《The Journal of biological chemistry》2012,287(19):15489-15501
12.
Hiroshi Ueda Jun-ichi Kurita Hiroyuki Neyama Yuuka Hirao Hiroyuki Kouji Tadashi Mishina Masaji Kasai Hirofumi Nakano Atsushi Yoshimori Yoshifumi Nishimura 《Bioorganic & medicinal chemistry letters》2017,27(20):4705-4709
The neuron-restrictive silencing factor NRSF/REST binds to neuron-restrictive silencing elements in neuronal genes and recruits corepressors such as mSin3 to inhibit epigenetically neuronal gene expression. Because dysregulation of NRSF/REST is related to neuropathic pain, here, we have designed compounds to target neuropathic pain based on the mSin3-binding helix structure of NRSF/REST and examined their ability to bind to mSin3 by NMR. One compound, mS-11, binds strongly to mSin3 with a binding mode similar to that of NRSF/REST. In a mouse model of neuropathic pain, mS-11 was found to ameliorate abnormal pain behavior and to reverse lost peripheral morphine analgesia. Furthermore, even in the less well epigenetically defined case of fibromyalgia, mS-11 ameliorated symptoms in a mouse model, suggesting that fibromyalgia is related to the dysfunction of NRSF/REST. Taken together, these findings show that the chemically optimized mimetic mS-11 can inhibit mSin3-NRSF/REST binding and successfully reverse lost peripheral and central morphine analgesia in mouse models of pain. 相似文献
13.
14.
15.
16.
Franciele Martini Marlon Régis Leite Suzan Gonçalves Rosa Isabella Pregardier Klann Cristina Wayne Nogueira 《Cell biochemistry and function》2020,38(2):213-221
Alzheimer's disease (AD) is a progressive neurodegenerative disorder that has generated scientific interest because of its prevalence in the population. Studies indicate that physical exercise promotes neuroplasticity and improves cognitive function in animal models and in human beings. The aim of the present study was to investigate the effects of strength exercise on the hippocampal protein contents and memory performance in mice subjected to a model of sporadic AD induced by streptozotocin (STZ). Swiss mice received two injections of STZ (3 mg/kg, intracerebroventricular). After 21 days, they began physical training using a ladde. Mice performed this protocol for 4 weeks. After the last exercise training session, mice performed the Morris Water Maze test. The samples of hippocampus were excised and used to determine protein contents of brain-derived neurotrophic factor (BDNF), extracellular signal-regulated kinase-Ca2+ (ERK), calmodulin-dependent protein kinase (CAMKII) and cAMP-response element-binding protein (CREB) signalling pathway. Strength exercise was effective against the decrease in the time spent and distance travelled in the target quadrant by STZ-injected mice. Strength exercise was also effective against the reduction of mature BDNF, tropomyosin receptor kinase B and neuronal nuclear antigen (NeuN) hippocampal protein levels in STZ mice. The decrease in the hippocampal ratio of pERK/ERK, pCAMKII/CAMKII and pCREB/CREB induced by STZ was reversed by strength exercise. Strength exercise decreased Bax/Bcl2 ratio in the hippocampus of STZ-injected mice. The present study demonstrates that strength exercise modulated the hippocampal BDNF/ERK-CAMKII/CREB signalling pathway and suppressed STZ-induced spatial memory impairment in mice. 相似文献
17.
18.
19.