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The CaaX motif directs C‐terminal protein modifications that include isoprenylation, proteolysis and carboxylmethylation. Proteolysis is generally believed to require either Rce1p or Ste24p. While investigating the substrate specificity of these proteases, using the yeast a‐factor mating pheromone as a reporter, we observed Rce1p‐ and Ste24p‐independent mating (RSM) when the CKQQ CaaX motif was used in lieu of the natural a‐factor CVIA motif. Uncharged or negatively charged amino acid substitutions at the a1 position of the CKQQ motif prevented RSM. Alanine substitutions at the a2 and X positions enhanced RSM. Random mutagenesis of the CaaX motif provided evidence that RSM occurs with approximately 1% of all possible CaaX motif permutations. Combined mutational and genetic data indicate that RSM‐promoting motifs have a positively charged amino acid at the a1 position. Two of nine naturally occurring yeast CaaX motifs conforming to this pattern promoted RSM. The activity of the isoprenylcysteine carboxyl methyltransferase Ste14p was required for RSM, indicating that RSM‐promoting CaaX motifs are indeed proteolysed. RSM was enhanced by the overexpression of Axl1p or Ste23p, suggesting a role for these M16A subfamily metalloproteases in this process. We have also determined that an N‐terminal extension of the a‐factor precursor, which is typically removed by the yeast M16A enzymes, is required for optimal RSM. These observations suggest a model that involves targeting of the a‐factor precursor to the peptidosome cavity of M16A enzymes where subsequent interactions between RSM‐promoting CaaX motifs and the active site of the M16A enzyme lead to proteolytic cleavage. Copyright © 2009 John Wiley & Sons, Ltd.  相似文献   

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One of the main functions of L-arginine (ARG) is the synthesis of nitric oxide (NO). NO is an important regulator of physiological processes in the central nervous system (CNS). NO promotes optimal cerebral blood flow, consolidates memory processes, facilitates long-term potentiation, maintains sleep-wake cycles, and assists in normal olfaction. However, at pathological levels, NO adversely affects brain function producing nitroxidative stress and promoting development of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and other disorders of the CNS. This review summarizes current knowledge of the role of NO in the CNS and the role of diet in regulating the levels of NO.  相似文献   

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Alzheimer's disease (AD) and Parkinson's diseases (PD) are the two most common progressive neurodegenerative diseases with limited knowledge on their cause and, presently, have no cure. There is an existence of multiple treatment methods that target only the symptoms temporarily and do not stop the progression or prevent the onset of disease. Neurodegeneration is primarily attributed to the natural process of aging and the deleterious effects of heightened oxidative stress within the brain, whether via direct or indirect mechanisms. Emerging evidence suggests that certain nutritional aspects play a crucial role in the prevention and management of neurodegenerative diseases. Lutein, a dietary carotenoid, has been studied for its antioxidant properties for more than a decade with several applications against age-related macular degeneration. It is high antioxidant potential and selective accumulation in the brain makes it a versatile compound for combatting various neurodegenerative diseases. In this review, the studies exhibiting neuroprotective properties of lutein against neurodegenerative conditions, more specifically AD and PD in various model systems as well as clinical observations have been reviewed. Accordingly, the concerns associated with lutein absorption and potential strategies to improve its bioavailability have been discussed.  相似文献   

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目的 研究6种茶叶提取物的乙酰胆碱酯酶抑制活性。方法 采用改良的Ellman酶促反应来检测乙酰胆碱酯酶的活性, 以乙酰胆碱酯酶的活性为指标, 计算乙酰胆碱酯酶抑制率。结果 6种茶叶均具有不同程度的乙酰胆碱酯酶抑制活性。当萃取物浓度为1 mg/mL时, 宁红茶表现出很强的乙酰胆碱酯酶抑制活性, 平均抑制率高达64.41%。云台山毛尖和靖安白茶抑制率较高均在50%以上, 分别为56.27%和54.42%。狗牯脑、庐山云雾茶和铁观音抑制率分别为34.53%、29.62%、21.47%。当萃取物浓度下降为0.1 mg/mL时, 萃取物抑制活性有明显下降, 6种茶的平均抑制率均小于30%。结论 6种茶叶中云台山毛尖、宁红茶和靖安白茶有较强的乙酰胆碱酯酶抑制活性, 可为开发相关的功能性食品提供参考。  相似文献   

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目的:探究阿尔茨海默病与日常膳食的关系,可为科学饮食,降低患阿尔茨海默病的风险提供参考.方法:采用病例对照的研究方法,选取黑龙江省农垦地区9个管理局的66家敬老院,65岁以上且未患过脑血管性疾病的老年人作为研究对象,其中阿尔茨海默病病例组256人,健康对照组408人,对其进行问卷调查.结果:文化程度高、非独居的研究对象...  相似文献   

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Alzheimer's disease (AD), a progressiveneurodegenerative condition is marked by extensive damage in the brain and dementia. Among the pathological hallmarks of AD is beta-amyloid (Aβ). Production of toxic Aβ oligomers production and accumulation in the brain is among the characteristic features of the disease. The abnormal accumulation Aβ is initiated by the catalytic degradation of Amyloid Precursor Proteins (APP) by Beta Amyloid Cleaving Enzyme 1 (BACE1) to generate insoluble amyloid plaques. The abnormal proteins are mitochondrial poison which disrupt the energy production and liberate excessive free radicals causing neuronal damage and mutations. Consequently, targeting Aβ-associated pathways has become a focus in the pursuit of developing effective AD treatments. An obstacle faced by many medications used to treat neurodegenerative diseases (NDs) is the restricted permeability across the blood-brain barrier (BBB). Unfortunately, no anti-amyloid drug is clinically approved till now. Recent advancements in nanotechnology have provided a possible solution for delivering medications to specific targets. By integrating natural products with nano-medicinal approaches, it is possible to develop novel and highly efficient therapeutic strategies for the treatment of AD.  相似文献   

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Recent evidence has indicated that a group of plant‐derived compounds known as flavonoids may exert particularly powerful actions on mammalian cognition and may reverse age‐related declines in memory and learning. In addition, growing evidence is also suggestive that flavonoids may delay the development of Alzheimer's disease‐like pathology, suggestive of potential dietary strategies in dementia. Although these low‐molecular‐weight phytochemicals are absorbed to only a limited degree, they have been found to counteract age‐related cognitive declines possibly via their ability to interact with the cellular and molecular architecture of the brain responsible for memory. However, the majority of the research has been carried out at rather supraphysiological concentrations and only a few studies have investigated the neuromodulatory effects of physiologically attainable flavonoid concentrations. This review will summarize the evidence for the effects of flavonoids and their metabolites in age‐related cognitive decline and Alzheimer's disease. Mechanisms of actions will be discussed and include those activating signalling pathways critical in controlling synaptic plasticity, reducing neuroinflammation and inducing vascular effects potentially capable of causing new nerve cell growth in the hippocampus. Altogether, these processes are known to be important in maintaining optimal neuronal function, to limit neurodegeneration and to prevent or reverse age‐dependent deteriorations in cognitive performance. © 2013 Society of Chemical Industry  相似文献   

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对人参水溶性总蛋白对β-淀粉样蛋白所致人神经母细胞瘤SH-SY5Y损伤的影响及其作用机制进行研究。使用25μmol/L老化后Aβ_(25-35)处理SH-SY5Y细胞建立阿尔兹海默病体外模型;用人参水溶性总蛋白(6.25、12.5、25μg/mL)预保护SH-SY5Y细胞12 h,随后加入25μmol/L的Aβ_(25-35)共同孵育24 h;CCK-8法检测细胞活力;流式细胞术检测细胞凋亡、抑制活性氧(reactive oxygen species,ROS)水平和线粒体膜电位变化;紫外分光光度法检测三磷酸腺苷(adenosine 5'-triphosphate,ATP)、丙二醛(malondialdehyde,MDA)含量、超氧化物歧化酶(superoxide dismutase,SOD)活力;蛋白免疫印迹法检测细胞色素C释放以及凋亡相关蛋白B淋巴细胞瘤-2基因(B-cell lymphoma-2,Bcl-2)、Bcl-2相关X蛋白(Bcl-2 associated X protein,Bax)表达。结果显示SH-SY5Y细胞经Aβ_(25-35)诱导后,细胞活力显著降低,凋亡程度严重增加(P0.000 1);不同浓度的人参总蛋白可以挽救Aβ_(25-35)诱导所致细胞活力降低和凋亡程度增加,并呈现浓度依赖性;人参总蛋白预处理可以降低Aβ_(25-35)诱导的线粒体超氧化物升高,ROS产生,显著抑制Aβ_(25-35)损伤导致的线粒体膜电位(mitochondrial membrane potential,MMP)降低和三磷酸腺苷水平的下降;人参总蛋白可抑制Aβ_(25-35)所致的细胞色素C向胞质的释放,下调Bax表达、上调Bcl-2表达。  相似文献   

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The nucleolar Mak16p protein of Saccharomyces cerevisiae has been implicated in 60S ribosome biogenesis. To learn more about the role of Mak16p in this process, ribosomal RNA processing was examined in a mak16-1 temperature-sensitive yeast strain. Steady-state levels of the 25S and 5.8S mature rRNA species dropped dramatically over a 4 h period in the mak16-1 yeast after a shift to the non-permissive temperature, while 18S and 5S rRNA levels decreased only moderately. Ribosomal RNA processing (rRNA) analyses showed that the most prominent defect at the non-permissive temperature was a dramatic decrease in 27SB precursor RNA levels, with no significant increase in the levels of any precursor. These data indicate an essential role for Mak16p in the stability of the 27SB precursor rRNA. Association of Mak16p with the 66S preribosomal complex does not appear to be sufficient for its function, because the mutant Mak16-1p protein was detected in sucrose density gradient fractions corresponding to the 66S pre-RNP complex.  相似文献   

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随着社会老龄化的加剧,阿尔兹海默症已成为威胁人类健康的重大疾病之一,该病发病机制复杂,目前尚无有效疗法。饮食护理在阿尔兹海默症的治疗过程中发挥着重要作用。本文从阿尔兹海默症的概念、表现症状、发病危险因素、患者的饮食护理以及膳食禁忌等进行综述,以期为阿尔兹海默症患者的护理提供理论依据,提高患者的生存质量。  相似文献   

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Alzheimer's disease (AD) has been a challenge and hotspot in the field of neuroscience research due to the high morbidity. As we all know, walnut kernel (WK) ingestion has been linked to benefits to brain health and has the function of improving memory. This study follows the AD model induced by scopolamine to reveal the active fractions and substances of walnut in the treatment of AD.  相似文献   

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Quercetin (3,3′,4′,5,7‐pentahydroxyflavone) is found in vegetables and fruits. It is one of the major flavonoids that is part of human diets. Quercetin has several pharmacological effects in the nervous system as a neuroprotective agent. In this review, we summarize the research on quercetin and its role in memory in both animals and humans. Articles were chosen from the Scopus, PubMed, and Web of Science databases. In this review, we describe and summarize the importance of quercetin's presence in the body, particularly in the brain; its kinetics, including its absorption, metabolism, distribution, and excretion; its behavioral effects; and some of the possible mechanisms of action of quercetin on memory in different animal models. Several important pathways that may be involved in the processes of learning and memory, long‐term potentiation, and cognition may be impaired during neurological diseases or other medical conditions. As dietary quercetin is important, provision of its best formulation for delivery to the brain as a nutraceutical and in clinical translational research for the prevention or treatment of Alzheimer's disease and other types of dementia is necessary.  相似文献   

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目的:虾青素是海洋食品中大量存在的一种类胡萝卜素,其抗氧化性被广泛认可。近年来,氧化应激对阿尔茨海默病(AD)的影响研究受到越来越多的关注。以往研究主要关注AD发病后,利用虾青素的抗氧化功效延缓其病理进程。本文旨在通过快速老化小鼠模型探究虾青素对AD的预防作用。方法:将雄性快速老化小鼠(SAMP8)随机分为模型组、虾青素组,虾青素灌胃剂量为40 mg/kg bw,干预4个月,抗快速老化小鼠(SAMR1)作为正常对照组。利用水迷宫实验、旷场实验评价小鼠的学习记忆能力和焦虑情绪的变化,并测定脑部海马、肝脏以及血清中β-淀粉样蛋白(Aβ)含量和氧化应激指标。结果:虾青素能显著提高SAMP8小鼠的学习记忆能力,缓解焦虑;同时虾青素能显著减少脑内Aβ的含量,改善脑内氧化应激水平,在肝脏和血清中也显示不同程度的抗氧化水平。结论:膳食虾青素可能通过抑制脑内和组织中的氧化应激来提高快速老化小鼠学习记忆能力,预防或延缓AD的发生。本研究结果为探究虾青素的神经保护功能及其在相关功能性食品或膳食补充剂的应用提供理论参考。  相似文献   

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