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）
立项年度
2（略）
立项时间
未（略）
项目编号
8（略）1（略）
项目级别
国（略）
研究期限
未（略） （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. „Status and trends in the development of clinical diagnostic agents“,WIREs Nanomed Nanobiotechnol,9(2017)
2.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.
...3. 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.
4. Type: Conference Papers and Presentations Status: Published Year Published: 2012 Citation: Laible, G. (2012). Conference VIII. Transgenic Res, 21, 901-925.
5.Dysregulation of long non-coding RNAs and their mechanisms in Huntington's disease
- 关键词：
- Huntington' s disease; lncRNA; mHTT; polyQ; RNA;GENE-EXPRESSION; BDNF-AS; NEUROTROPHIC FACTOR; MUTANT HUNTINGTIN;IN-VIVO; BEHAVIORAL ABNORMALITIES; MOLECULAR PATHOGENESIS; ALTEREDEXPRESSION; FUNCTIONAL-ROLE; CELL APOPTOSIS
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.
...6.MicroRNAs Dysregulation and Metabolism in Multiple System Atrophy
- 关键词：
- microRNA; multiple system atrophy; alpha-synuclein; autophagy;neuroinflammation;ALPHA-SYNUCLEIN EXPRESSION; PARKINSONS-DISEASE; NEURODEGENERATIVEDISEASES; CYTOPLASMIC INCLUSIONS; HUNTINGTONS-DISEASE; ALTEREDEXPRESSION; UP-REGULATION; MOUSE MODEL; NEUROINFLAMMATION; ACTIVATION
Multiple system atrophy (MSA) is an adult onset, fatal disease, characterized by an accumulation of alpha-synuclein (alpha-syn) in oligodendroglial cells. MicroRNAs (miRNAs) are small non-coding RNAs involved in post-translational regulation and several biological processes. Disruption of miRNA-related pathways in the central nervous system (CNS) plays an important role in the pathogenesis of neurodegenerative diseases, including MSA. While the exact mechanisms underlying miRNAs in the pathogenesis of MSA remain unclear, it is known that miRNAs can repress the translation of messenger RNAs (mRNAs) that regulate the following pathogenesis associated with MSA: autophagy, neuroinflammation, alpha-syn accumulation, synaptic transmission, oxidative stress, and apoptosis. In this review, the metabolism of miRNAs and their functional roles in the pathogenesis of MSA are discussed, thereby highlighting miRNAs as potential new biomarkers for the diagnosis of MSA and in increasing our understanding of the disease process.
...7.The Emerging Role of microRNAs in Polyglutamine Diseases
- 关键词：
- microRNAs; polyglutamine diseases; biomarker; neurodegeneration; therapy;HUNTINGTONS-DISEASE; CELLULAR-MODEL; GENE; ATAXIA; MUTANT;DYSREGULATION; SUPPRESSION; EXPRESSION; BIOMARKERS; NEUROGENESIS
MicroRNAs (miRNAs) are small non-coding molecules that regulate a large amount of post-transcriptional repressor genes by recognizing semi-complementary target sequences that are normally located in the 3' UTR of the mRNA. Altered expression of miRNA has been related to several pathological processes, including polyglutamine (Poly Q) diseases. Specific expression patterns in the circulating fluids and brain parenchyma have been speculated as potential biomarkers for Poly Q disease diagnosis and prognosis. Several miRNAs have been consistently identified in diseases including Huntington's disease (HD) and spinocerebellar ataxia (SCA). In our review, we describe the emerging role of miRNAs in Poly Q diseases and provide an overview on general miRNA biology, implications in pathophysiology, and their potential roles as future biomarkers and applications for therapy.
...8.LOX-1 and atherosclerotic-related diseases
Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), a scavenger receptor of oxidized low-density lipoprotein (ox-LDL) found in various cells, plays a crucial role in the formation and progression of atherosclerotic plaques. Animal studies have suggested that LOX-1 mediates the balance between internalization and degeneration of endothelial cells, thereby contributing to various steps in the atherosclerotic process, from initiation to plaque rupture. Under pathological conditions, the extracellular domain of membrane bound LOX-1 can be largely proteolytically cleaved into a soluble form (sLOX-1), which is proportional and linked to the LOX-1 expression level. Circulating levels of sLOX-1 are regarded as a risk biomarker for plaque rupture and acute coronary syndrome (ACS). Recently, studies have shown that sLOX-1 is also elevated in patients with acute stroke and can be a predictive biomarker for acute stroke. With the discovery of the vital role of LOX-1 in atherosclerosis, there is growing focus on the influence of LOX-1 in atherosclerotic-related diseases, including coronary arterial disease(CAD), stroke, and other cardiovascular events. Genetic polymorphisms of LOX-1 have been investigated and have been found to modulate the risk of these diseases. Most polymorphisms have been found to be risk factors, except for the splicing isoform LOXIN. This review concludes with a discussion of the potential future applications of LOX-1 for atherosclerotic-related diseases.
...9.LOX-1 and atherosclerotic-related diseases
- 关键词：
- LOX-1; Coronary arterial disease; Stroke;LOW-DENSITY-LIPOPROTEIN; OXIDIZED LDL RECEPTOR-1;CORONARY-ARTERY-DISEASE; LECTIN-LIKE; OLR1 GENE; ISCHEMIC-STROKE;3'-UTR-C188T POLYMORPHISMS; ENDOTHELIAL RECEPTOR; SPLICING ISOFORM;ASSOCIATION
Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), a scavenger receptor of oxidized low-density lipoprotein (ox-LDL) found in various cells, plays a crucial role in the formation and progression of atherosclerotic plaques. Animal studies have suggested that LOX-1 mediates the balance between internalization and degeneration of endothelial cells, thereby contributing to various steps in the atherosclerotic process, from initiation to plaque rupture. Under pathological conditions, the extracellular domain of membrane bound LOX-1 can be largely proteolytically cleaved into a soluble form (sLOX-1), which is proportional and linked to the LOX-1 expression level. Circulating levels of sLOX-1 are regarded as a risk biomarker for plaque rupture and acute coronary syndrome (ACS). Recently, studies have shown that sLOX-1 is also elevated in patients with acute stroke and can be a predictive biomarker for acute stroke. With the discovery of the vital role of LOX-1 in atherosclerosis, there is growing focus on the influence of LOX-1 in atherosclerotic-related diseases, including coronary arterial disease(CAD), stroke, and other cardiovascular events. Genetic polymorphisms of LOX-1 have been investigated and have been found to modulate the risk of these diseases. Most polymorphisms have been found to be risk factors, except for the splicing isoform LOXIN. This review concludes with a discussion of the potential future applications of LOX-1 for atherosclerotic-related diseases.
...10.Reversible splenial lesion syndrome associated with acute Mycoplasma pneumoniae-associated encephalitis: A report of four cases and literature review
- 关键词：
- Mycoplasma pneumoniae-associated encephalitis; reversible spleniallesion syndrome; magnetic resonance imaging; serum antibody;CLINICALLY MILD ENCEPHALITIS/ENCEPHALOPATHY; NERVOUS-SYSTEMCOMPLICATIONS; CHILDHOOD ENCEPHALITIS; BRAIN-STEM; INFECTIONS;MANIFESTATIONS; DIAGNOSIS; ENCEPHALOPATHY; PCR
Reversible splenial lesion syndrome (RESLES) is a rare clinico-radiological syndrome that is defined as reversible lesions that involve the splenium of the corpus callosum (SCC). RESLES has been reported in patients with a broad spectrum of diseases and conditions, including infections, hypoglycemia and poisoning. The present report described four RESLES cases triggered by Mycoplasma pneumoniae (M. pneumoniae) and discussed the associated diagnostic challenges. Four cases of acute M. pneumoniae-associated encephalitis that displayed RESLES were reviewed. The clinical presentations were nonspecific in these patients. However, magnetic resonance imaging (MRI) revealed consistent lesions in the SCC with a hyperintensity in diffusion-weighted imaging (DWI) and hypointensities in T1WI, which disappeared after a variable lapse. Treatment with azithromycin or combined treatment with immunomodulatory agents if necessary led to a good prognosis. The present findings indicated that radiological diagnosis of RESLES should be considered in patients with M. pneumoniae-associated encephalitis. Furthermore, serum Mycoplasma antibody is important for the diagnosis of M. pneumoniae-associated encephalitis.
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