CCAAT增强子结合蛋白同源蛋白在多聚谷氨酰胺疾病分子发病机制中的作用
项目来源
国（略）科（略）(（略）C（略）
项目主持人
丛（略）
项目受资助机构
中（略）大（略）
项目编号
8（略）1（略）
立项年度
2（略）
立项时间
未（略）
研究期限
未（略） （略）
项目级别
国（略）
受资助金额
7（略）0（略）
学科
医（略）-（略）统（略）系（略）与（略）常
学科代码
H（略）9（略）9（略）
基金类别
面（略）
关键词
转（略）异（略） （略）应（略） （略）氨（略）病（略）C（略）T（略）结（略） （略）亡（略）;（略）l（略）u（略）i（略）d（略）a（略） （略）C（略） （略）a（略）r（略）n（略）g（略）o（略）n（略）m（略）g（略） （略）t（略） （略）r（略）c（略）t（略）a（略）e（略）u（略）i（略）;（略）d（略）a（略）c（略）t（略）l（略）;（略）o（略）t（略）p（略）w（略）
参与者
冯（略）剑（略）辉（略）川（略）；（略）；（略）
参与机构
中（略）大（略）
项目标书摘要：单基（略）胺(PolyQs)（略）际上神经病学的研究（略）网应激和未折叠蛋白（略）期事件，本课题基于（略）因子CCAAT增强（略）HOP)的转录及蛋（略）导的内质网应激和未（略），并在细胞核内大量（略）舞蹈病(HD)和脊（略）CA3)的细胞模型（略）检测、免疫共沉淀、（略）光、lightCy（略）胞成分分析来研究变（略）HOP转录水平增高（略）yQs对CHOP转（略）制，以及PolyQ（略）凋亡通路作用的影响（略）P siRNA干预（略）下调CHOP水平可（略）蛋白毒性作用。
Applicati（略）: The stu（略）athogenes（略）lutamine(（略）ases caus（略）e-gene mu（略）n interna（略）arch focu（略）ogy.Recen（略）ound the （略） reticulu（略） stress)a（略）lded prot（略）e(UPR)are（略）ts in Pol（略）s.Based o（略）ngs that （略）onal and （略）els of CC（略）ng bindin（略）omologous（略）OP),a tra（略）l facor,a（略） in PolyQ（略）R stress （略） accumula（略）cally in （略）,this pro（略）o study p（略）tream reg（略）hanism un（略）e elevate（略） level in（略）o PolyQs （略）e effect （略）n the tra（略）l activit（略）nd the po（略）rlying me（略） well as （略） of polyQ（略）n CHOP-in（略）otic path（略）ington's （略）and spino（略）ataxia ty（略）ell model（略）gene tran（略）ciferase （略）ne detect（略）noprecipi（略）matin imm（略）ation,imm（略）ence,ligh（略） and sub-（略）mponents （略）e project（略）to study （略）e rescue （略）down regu（略）HOP by us（略）RNA on cy（略）of polyQ （略）
项目受资助省
辽（略）
项目结题报告(全文)
单基因变异导致的多（略）s)疾病发病机制的（略）研究热点。异常扩增（略）致至少9种遗传性神（略）舞蹈病(HD)。P（略）的分子机制尚不明确（略）、内质网应激和未折（略）s疾病分子发病机制（略）究发现PolyQs（略）一个新的靶蛋白，重（略）因子――CCAAT（略）(CHOP),同时（略）测、免疫共沉淀、染（略）光、lightCy（略）胞成分分析来研究变（略）蛋白对影响CHOP（略）性的可能分子机制。（略）录调节、内质网应激（略）重要调节作用。研究（略）白和变异htt 蛋（略）RNA转录水平和蛋（略）蛋白在包涵体形成之（略）表达水平。重要的是（略）也发现CHOP蛋白（略）照。研究发现变异亨（略）P上游转录调控因子（略）F4),与CHOP（略）相互结合，可能是变（略）P转录水平的分子机（略）蛋白影响内源性CH（略）其大量聚集在细胞核（略）CHOP蛋白的磷酸（略）诱导的转录因子，其（略）平增高会影响其转录（略）。因此，通过变异亨（略）CHOP通路的失衡（略）多聚谷氨酰胺疾病的（略）用。干预ATF4-（略）谷氨酰胺疾病的转录（略）
1.Ubiquitin specific peptidase 11 knockdown slows Huntington's disease progression via regulating mitochondrial dysfunction and neuronal damage depending on PTEN-mediated AKT pathway.
- 关键词：
- EC 3.1.3.67 / PTEN Phosphohydrolase. EC 2.7.11.1 / Proto-Oncogene Proteins c-akt. EC 3.1.2.- / Thiolester Hydrolases;Huntingtons disease (HD); Mitochondria; Neuronal apoptosis; Phosphatase and tensin homolog (PTEN); Ubiquitin specific peptidase 11 (USP11)
- Gao, Bai;Jing, Yuchen;Li, Xi;Cong, Shuyan
- 《Molecular medicine 》
- 2025年
- 31卷
- 1期
- 期刊
BACKGROUND: Mitochondrial dysfunction and neuronal damage are major sign of cytopathology in Huntington's disease (HD), a neurodegenerative disease. Ubiquitin specific peptidase 11 (USP11) is a deubiquitinating enzyme involved in various physiological processes through regulating protein degradation. However, its specific role in HD is unclear.; METHODS: To interfere with USP11 expression, adeno-associated viruses 2 containing USP11-specific shRNA were injected into the bilateral striatum of 12-week-old R6/1 and WT mice. In vitro, the inducible PC12 cell model of HD was used in which the expression of an N-terminal truncation of huntingtin, with either wild type (Q23) or expanded polyglutamine (Q74) can be induced by the doxycycline. USP11 was knocked down to study its role in HD. The protein expression patterns in Q74 cells were quantified by label-free proteomics to further explore the target protein of USP11. Detecting the association between USP11 and Phosphatase and Tensin Homolog (PTEN) through Co-IP.; RESULTS: Herein, USP11 was found to be upregulated in the striatum of R6/1 mice (an HD model with gradual development of symptoms) in an age-dependent manner. The spontaneous HD was alleviated by silencing USP11, as evidenced by improved locomotor activity and spatial memory, attenuated striatal atrophy in R6/1 mice, reduced accumulation of mutant huntingtin protein, and restored mitochondrial function in vitro and in vivo. The results of label-free proteomics revealed a significant change in the protein expression profile. Through functional enrichment, we focused on PTEN, known as a negative regulator of the AKT pathway. We demonstrated that USP11 downregulation promoted ubiquitination modification of PTEN and activated the AKT pathway, and PTEN overexpression reversed the effects of USP11 knockdown.; CONCLUSIONS: Collectively, USP11 knockdown protects R6/1 mouse neurons from oxidative stress by alleviating mitochondrial dysfunction, thereby preventing the HD progression. This is achieved by inhibiting PTEN expression, which in turn activates the AKT pathway. This study suggests that USP11-PTEN-AKT signaling pathway may be a new attractive therapeutic target for HD. © 2025. The Author(s).
...2.Reversible splenial lesion syndrome associated with acute Mycoplasma encephalitis:a report of four cases
- Dong xiaoyu；Cong Shuyan；
- 0年
- 卷
- 期
- 期刊
3. „Status and trends in the development of clinical diagnostic agents“,WIREs Nanomed Nanobiotechnol,9(2017)
4.Levels of iron and iron-related proteins in Alzheimer's disease: A systematic review and meta-analysis
- 关键词：
- Iron; Ferritin; Lactoferrin;FERRITIN; SERUM
Background and purpose: Iron homeostasis disturbance has been suggested to play a role in the pathology of Alzheimer's disease (AD). Systemic iron levels are regulated by iron-related proteins, such as ferritin and transferrin. This meta-analysis was established to evaluate iron and iron-related proteins (ferritin, transferrin, lactoferrin, haptoglobin, hepcidin) in cerebrospinal fluid (CSF) and blood samples of AD patients compared with those in healthy controls (HCs).Methods: Iron and iron-related proteins in Alzheimer's disease was systematically searched within five databases (PubMed, EMBASE, Web of Science, Cochrane, Scopus) up to October 23, 2022. Fifty-four studies (with data for 5105 participants: 2174 AD patients and 2931 HCs) were included in this meta-analysis. This study was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA), applying Stata 14.0 software. Results: Decreased iron in blood and increased ferritin in CSF were found in AD patients compared with the levels in HCs. AD patients also exhibited lower lactoferrin in serum. Other variables (iron in CSF, ferritin in blood, transferrin in CSF/blood, haptoglobin in CSF/blood, and hepcidin in blood) did not differ between the groups.Conclusion: This meta-analysis indicated that iron and iron-related proteins were associated with the risk of AD, suggesting the value of further exploration of iron imbalance in AD using biofluids.
...5. Vetemaa, M.; Eschbaum, R.; Albert, A.; Saat, T. (2005). Distribution, sex ratio and growth of Carassius gibelio (Bloch) in coastal and inland waters of Estonia (north-eastern Baltic Sea). Journal of Applied Ichthyology, 21 (4), 287−291.
6. Type: Conference Papers and Presentations Status: Published Year Published: 2012 Citation: Laible, G. (2012). Conference VIII. Transgenic Res, 21, 901-925.
7.颅神经受累的吉兰-巴雷谱系疾病35例临床分析
- 关键词：
- 吉兰-巴雷谱系疾病 颅神经 Miller-Fisher综合征 抗GQ1b抗体 基金资助：国家自然科学基金（81371271）； 辽宁省“百千万人才工程”资助项目（辽百千万立项[2015]41号）； 专辑：医药卫生科技 专题：神经病学 分类号：R745.43 手机阅读
- 盖晴;冷昶木;丛树艳
- 0年
- 卷
- 期
- 期刊
目的探讨吉兰-巴雷谱系疾病中颅神经受累的临床特点。方法回顾性分析2016年1月至2017年9月期间我科收治的35例颅神经受累的吉兰-巴雷综合征（GBS）患者的临床资料,进行亚组分类,分析各亚组中颅神经受损特点。结果 35例患者中,经典型GBS13例,Miller-Fisher综合征（MFS）9例,多颅神经型8例,急性眼外肌麻痹型2例,MFS与GBS重叠型2例,Bickerstaff脑干脑炎与GBS重叠型1例。经典型GBS以面神经受累最常见,MFS以展神经受累最常见,多颅神经型GBS以舌咽、迷走神经受累最常见。15例患者行神经节苷酯抗体检测,11例（73%）GQ1b抗体阳性。24例接受3个月的随访,仅1例仍有复视,其余患者颅神经症状均消失。结论吉兰-巴雷谱系疾病亚组间颅神经受损特点不同,眼外肌麻痹的患者多伴GQ1b抗体阳性。免疫治疗后颅神经症状多为可逆,预后良好。
...8.关注遗传性帕金森病
- 关键词：
- 帕金森病;遗传;治疗
- 谭小平;丛盛日;向春晨;丛树艳
- 《中国实用内科杂志》
- 2022年
- 卷
- 04期
- 期刊
帕金森病是一种多病因导致的神经系统退行性运动障碍性疾病，其中遗传因素是一个重要的原因，通常表现为早发和非典型症状。迄今为止，在家族性和部分散发性帕金森病患者中鉴定出超过20余个基因变异和100余个具有独立风险的位点突变，主要涉及的机制包括突触胞吐和内吞作用的缺陷、囊泡运输、溶酶体介导的自噬和线粒体维持功能障碍等。识别这些遗传变异可能会为药物开发和未来旨在改善疾病的临床试验提供分子基础，有助于开发神经保护治疗和疾病修饰疗法。
...9.Bi-Basal Ganglia Involvement with Signal Evolution in a Case of Anti-LGI1 Encephalitis
- 关键词：
- Antithyroid antibody; faciobrachial dystonic seizures; Hashimotoencephalopathy; leucine-rich glioma-inactivated 1; magnetic resonanceimaging
- Gai, Qing;Ruan, Shan;Dong, Xiaoyu;Cong, Shuyan
- 《NEUROLOGY INDIA》
- 2022年
- 70卷
- 1期
- 期刊
Anti-leucine- rich glioma-inactivated 1 (LGI1) encephalitis is a rare type of non-paraneoplastic limbic encephalitis (LE) mainly characterized by seizures, cognitive disorder, faciobrachial dystonic seizures (FBDS), hyponatremia, insomnia, and autonomic dysfunction. Here, we report the case of an elderly female patient who tested positive for antibodies against LGI1 and was initially thought to have Hashimoto encephalopathy (HE) due to its similar clinical features and the patient's high titers of antithyroid antibody. Interestingly, during the course of the disease, the patient exhibited typical FBDS and brain magnetic resonance imaging (MRI) showed a hyperintense signal evolution from T2./Fluid attenuated inversion recovery (FLAIR) to T1-weighted image in the bilateral basal ganglia (BG), which have rarely been reported previously.
...10.Dysregulation of long non-coding RNAs and their mechanisms in Huntington's disease
- 关键词：
- GENE-EXPRESSION; BDNF-AS; NEUROTROPHIC FACTOR; MUTANT HUNTINGTIN; IN-VIVO; BEHAVIORAL ABNORMALITIES; MOLECULAR PATHOGENESIS; ALTERED EXPRESSION; FUNCTIONAL-ROLE; CELL APOPTOSIS
- Tan, Xiaoping;Liu, Yang;Liu, Yan;Zhang, Taiming;Cong, Shuyan
- 《JOURNAL OF NEUROSCIENCE RESEARCH》
- 2021年
- 99卷
- 9期
- 期刊
Extensive alterations in gene regulatory networks are a typical characteristic of Huntington's disease (HD); these include alterations in protein-coding genes and poorly understood non-coding RNAs (ncRNAs), which are associated with pathology caused by mutant huntingtin. Long non-coding RNAs (lncRNAs) are an important class of ncRNAs involved in a variety of biological functions, including transcriptional regulation and post-transcriptional modification of many targets, and likely contributed to the pathogenesis of HD. While a number of changes in lncRNAs expression have been observed in HD, little is currently known about their functions. Here, we discuss their possible mechanisms and molecular functions, with a particular focus on their roles in transcriptional regulation. These findings give us a better insight into HD pathogenesis and may provide new targets for the treatment of this neurodegenerative disease.
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