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Neuroprotection - New Approaches and Prospects最新文献

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Alzheimer’s Disease Neuroprotection: Associated Receptors 阿尔茨海默病神经保护:相关受体
Pub Date : 2020-03-28 DOI: 10.5772/intechopen.91918
Alice Barros Câmara
Research with humans and animals has been developed over the past few years to identify receptors involved in Alzheimer’s disease, aiming at a better understanding of the mechanisms and pathophysiological aspects associated with the disease. Such receptors, whether or not directly associated with current AD therapy, are relevant since their blockage or activation might result in improving or worsening the clinical scenario of the disease. In other words, such receptors might be involved in the AD prognosis. This chapter discusses some relevant points about the receptors involved with AD.
在过去的几年里,人类和动物的研究已经发展到确定与阿尔茨海默病有关的受体,旨在更好地了解与该疾病相关的机制和病理生理方面。这些受体,无论是否与当前的AD治疗直接相关,都是相关的,因为它们的阻断或激活可能导致疾病的临床情况改善或恶化。换句话说,这些受体可能与AD的预后有关。本章讨论了与AD相关的受体。
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引用次数: 0
Neuroprotective and Neurorestorative Properties of Copolymer-1: Its Immunomodulating Effects on Ischemic Stroke 共聚物-1的神经保护和神经恢复特性:其对缺血性脑卒中的免疫调节作用
Pub Date : 2020-03-02 DOI: 10.5772/intechopen.91343
María Yolanda Cruz Martínez, Melanie Tessa Saavedra Navarrete, José Juan Antonio Ibarra Arias
Stroke is a pathology of great relevance worldwide as it currently occupies the second motif of death and the third reason of disability. Although exits some therapies that are used successfully in the clinic, a very high percentage of patients do not have the opportunity to benefit from them; therefore, it is imperative to propose other alternatives that may favor more patients. In this chapter, we briefly review the inflammatory response induced by stroke and also its deleterious and protective effects. We will describe the characteristics of copolymer-1 and the effects that this compound has shown in models of cerebral ischemia.
中风是世界范围内具有重大意义的病理学,因为它目前占据了死亡的第二个主题和残疾的第三个原因。尽管有一些治疗方法在临床上成功使用,但很大比例的患者没有机会从中受益;因此,有必要提出其他可能有利于更多患者的替代方案。在本章中,我们简要回顾了脑卒中引起的炎症反应及其有害和保护作用。我们将描述共聚物-1的特性和这种化合物在脑缺血模型中显示的效果。
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引用次数: 0
Extracts and Essential Oils from Medicinal Plants and Their Neuroprotective Effect 药用植物提取物、精油及其神经保护作用
Pub Date : 2020-02-28 DOI: 10.5772/intechopen.90903
I. M. Costa, Elaine Cristina Gurgel Andrade Pedrosa, Ana Paula de Carvalho Bezerra, L. Fernandes, J. Cavalcanti, M. Freire, Dayane Pessoa de Araújo, Amália Cinthia Menezes Rêgo, I. Filho, Francisco Irochima Pinheiro, F. Guzen
Current therapies for neurodegenerative diseases offer only limited benefits to their clinical symptoms and do not prevent the degeneration of neuronal cells. Neurological diseases affect millions of people around the world, and the economic impact of treatment is high, given that health care resources are scarce. Thus, many therapeutic strategies to delay or prevent neurodegeneration have been the subject of research for treatment. One strategy for this is the use of herbal and essential oils of different species of medicinal plants because they have several bioactive compounds and phytochemicals with neuroprotective capacity. In addition, they respond positively to neurological disorders, such as dementia, oxidative stress, anxiety, cerebral ischemia, and oxidative toxicity, suggesting their use as complementary treatment agents in the treatment of neurological disorders.
目前对神经退行性疾病的治疗只对其临床症状提供有限的益处,并且不能防止神经元细胞的变性。神经系统疾病影响着全世界数百万人,鉴于卫生保健资源稀缺,治疗的经济影响很大。因此,许多延缓或预防神经退行性变的治疗策略一直是治疗研究的主题。其中一个策略是使用不同种类药用植物的草药和精油,因为它们含有几种具有神经保护能力的生物活性化合物和植物化学物质。此外,它们对神经系统疾病,如痴呆、氧化应激、焦虑、脑缺血和氧化毒性有积极的反应,这表明它们可以作为神经系统疾病治疗的补充治疗剂。
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引用次数: 1
An Alternate View of Neuroprotection with Peptides in Alzheimer’s Disease 阿尔茨海默病中多肽神经保护的另一种观点
Pub Date : 2020-02-19 DOI: 10.5772/intechopen.91065
S. King, C. Suphioglu
Neuroprotection plays a crucial role in everyday life, maintaining a clean environment in the central nervous system to allow for normal functioning. In Alzheimer’s disease and other neurodegenerative disorders, neuroprotection may have two roles. Under standard circumstances, the immune system protects the CNS, but sometimes it can exacerbate the pathophysiology of some diseases through neuroinflammation leading to further degeneration. Alzheimer’s disease is fast getting out of control, with no new approvals in therapeutics since 2003, and of those approved, all target symptomatic treatment. Initiated by a microglial response to Aβ plaques, therapeutic development should focus on the amyloid cascade as a neuroprotective measure for Alzheimer’s disease. This chapter will examine the status of the types of therapeutics in clinical trials for Alzheimer’s disease, offering insights into peptides as an area of opportunity for neuroprotection and detailing considerations for the use of peptides in Alzheimer’s disease.
神经保护在日常生活中起着至关重要的作用,维持中枢神经系统的清洁环境,使其正常运作。在阿尔茨海默病和其他神经退行性疾病中,神经保护可能有两个作用。在正常情况下,免疫系统会保护中枢神经系统,但有时免疫系统会通过神经炎症加剧某些疾病的病理生理,导致进一步退化。阿尔茨海默病正在迅速失去控制,自2003年以来,没有新的治疗方法获得批准,而这些批准的治疗方法都是针对对症治疗。由小胶质细胞对a β斑块的反应引发,治疗的发展应该集中在淀粉样蛋白级联作为阿尔茨海默病的神经保护措施。本章将研究阿尔茨海默病临床试验中治疗方法类型的现状,提供对多肽作为神经保护机会领域的见解,并详细说明在阿尔茨海默病中使用多肽的考虑。
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引用次数: 1
Glyproline Pro-Ampakine with Neuroprotective Activity 具有神经保护作用的甘脯氨酸亲安帕平
Pub Date : 2020-02-18 DOI: 10.5772/intechopen.91192
K. N. Koliasnikova, P. Povarnina, A. V. Tallerova, Yu. N. Firsova, Sergei V. Nikolaev, T. Antipova, A. Nadorova, L. Kolik, T. Gudasheva, S. Seredenin
Previously it was shown that neuropeptide cyclo-L-prolylglycine (CPG) is a positive modulator of AMPA receptors, which increases BDNF level in neuronal cell cultures. The spectrum of CPG’s pharmacological effects corresponds to that of BDNF. Dipeptide N-phenylacetyl-glycyl-L-proline ethyl ester (GZK-111) was designed and synthesized as a linear analog of CPG. The aim of the present work was to reveal the pharmacological profile of GZK-111. Dipeptide GZK-111 was shown to metabolize into CPG in vitro and increased cell survival by 28% at concentrations of 10-7–10-6 M in a Parkinson’s disease cell model. In a model of cerebral ischemia, GZK-111, at a dose of 0.5 mg/kg, i.p., was found to have neuroprotective effects, reducing the cerebral infarct volume by 1.6 times. Similar to CPG, GZK-111, at the range 0.1–1.0 mg/kg, i.p., possessed a stereospecific antiamnesic activity. A significant anxiolytic effect was observed at a dose of 1.5 mg/kg. GZK-111, at the range 0.5–4.0 mg/kg, i.p., demonstrated analgesic activity. GZK-111, at a dose of 10 mg/kg/7 days, i.p., possessed antidepressant-like activity. So, the neuroprotective, nootropic, antihypoxic, anxiolytic, antidepressant-like, and analgesic effects of GZK-111 were revealed. Thus, GZK-111 can be considered as a pharmacologically active pro-ampakine with a BDNF-ergic mechanism of action.
先前有研究表明,神经肽环- l -脯氨酸(CPG)是AMPA受体的正向调节剂,可提高神经细胞培养中BDNF的水平。CPG的药理作用谱与BDNF一致。设计合成了二肽n -苯乙酰-甘酰基- l-脯氨酸乙酯(GZK-111)作为CPG的线性类似物。本研究的目的是揭示GZK-111的药理学特征。二肽GZK-111在体外代谢成CPG,在帕金森病细胞模型中,浓度为10-7-10-6 M时,细胞存活率提高28%。在脑缺血模型中,GZK-111在0.5 mg/kg, i.p的剂量下具有神经保护作用,使脑梗死体积减少1.6倍。与CPG相似,GZK-111在0.1 ~ 1.0 mg/kg, i.p.范围内具有立体特异性抗遗忘活性。在1.5 mg/kg剂量下观察到显著的抗焦虑作用。GZK-111在0.5 ~ 4.0 mg/kg, i.p范围内表现出镇痛活性。GZK-111给药剂量为10mg /kg/7天,每日口服,具有抗抑郁样活性。因此,GZK-111具有神经保护、促智、抗缺氧、抗焦虑、类抗抑郁和镇痛作用。因此,GZK-111可被认为是一种具有bdnf -能作用机制的具有药理活性的亲氨pakine。
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引用次数: 4
Neuroprotective Potentials of Natural Vitamin E for Cerebral Small Vessel Disease 天然维生素E对脑血管疾病的神经保护作用
Pub Date : 2020-02-17 DOI: 10.5772/intechopen.91028
M. Mustapha, Che Mohd Nasril Che Mohd Nassir, Y. K. Hay, Fung Wai Yee, H. Hamid
Cerebral small vessel disease (CSVD) refers to a spectrum of clinical and neuroimaging findings resulting from pathological processes of various etiologies affecting cerebral arterioles, perforating arteries, capillaries, and venules. It is the commonest neurological problem that results in significant disability, but awareness of it remains poor. It affects over half of people over 65 years old and inflicts up to third of acute strokes, over 40% of dementia, and a significant decline in physical ability in otherwise asymptomatic, aging individuals. Moreover, the unifying theory for the pathomechanism of the disease remains elusive and hence the apparent ineffective therapeutic approaches. Given the growing literature for natural vitamin E (tocopherols and tocotrienols) as a potent antioxidant, this chapter attempts to consolidate the contemporary evidence to shed plausible insights on the neuroprotective potentials of natural vitamin E in addressing the heterogenous CSVD spectrum, in health and in disease.
脑小血管疾病(CSVD)是指各种病因影响脑小动脉、穿动脉、毛细血管和小静脉的病理过程所引起的一系列临床和神经影像学表现。它是最常见的神经系统疾病,会导致严重的残疾,但人们对它的认识仍然很差。65岁以上的老年人中有一半以上受到影响,多达三分之一的急性中风、40%以上的痴呆都是由它造成的,而且在没有症状的老年人中,它还会导致身体能力显著下降。此外,该疾病的病理机制的统一理论仍然难以捉摸,因此明显无效的治疗方法。鉴于越来越多的文献表明天然维生素E(生育酚和生育三烯醇)是一种有效的抗氧化剂,本章试图巩固当代的证据,以揭示天然维生素E在解决异质性CSVD谱、健康和疾病方面的神经保护潜力。
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引用次数: 3
Neuroprotection: The Way of Anti-Inflammatory Agents 神经保护:抗炎药的途径
Pub Date : 2020-01-03 DOI: 10.5772/intechopen.90509
Patrice Mendel Nzogang, M. Donkeng
Neurons are basic structural and functional units of the nervous system with major function being that of integration and interpretation of neuronal input or information. The lifespan of a nerve cell generally last throughout the individual lifetime. However, some physiologic or pathologic processes may affect the neuron causing premature death of this cell or tissue. This premature neurological death caused by pathologic circumstances is what we call neurotoxicity. The biochemical mechanisms put forward to explain neurotoxicity are not fully known. Nonetheless, whatever the mechanism involved, the outcome usually results in apoptosis, pyropoptosis, or necrosis. Examples of these mechanisms include excitotoxicity, oxidative stress, glial cell destruction, vascular interruptions, and inflammation. The idea about possibly protecting neurons against insults using pharmacologic means leads to the birth of the neuroprotection concept. This new concept has emerged based on ongoing research, suggesting it is possible through physical and pharmacological means to prevent or avoid neurotoxicity by the abovementioned mechanisms but with the exception of vascular interruption mechanisms. We will present in this chapter a synoptic view of the inflammatory mechanisms implicated in neurotoxicity and bring out the possible implications in neuroprotection.
神经元是神经系统的基本结构和功能单位,其主要功能是整合和解释神经元输入或信息。神经细胞的寿命通常贯穿于个体的一生。然而,一些生理或病理过程可能影响神经元,导致该细胞或组织过早死亡。这种由病理环境引起的神经系统过早死亡就是我们所说的神经毒性。用以解释神经毒性的生化机制尚不完全清楚。然而,无论其机制如何,其结果通常是细胞凋亡、热致死或坏死。这些机制的例子包括兴奋性毒性、氧化应激、胶质细胞破坏、血管中断和炎症。利用药理学手段保护神经元免受损伤的想法导致了神经保护概念的诞生。这一新概念是基于正在进行的研究而出现的,表明可以通过物理和药理学手段通过上述机制预防或避免神经毒性,但血管中断机制除外。在本章中,我们将简要介绍与神经毒性有关的炎症机制,并提出可能对神经保护的影响。
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引用次数: 1
Hydrogen Sulfide as a Factor of Neuroprotection during the Constitutive and Reparative Neurogenesis in Fish Brain 硫化氢在鱼脑构成性和修复性神经发生中的神经保护作用
Pub Date : 2019-12-24 DOI: 10.5772/intechopen.90547
E. V. Pushchina, A. A. Varaksin, D. Obukhov
The H2S-producing systems were studied in trout telencephalon, tectum, and cerebellum at 1 week after eye injury. The results of ELISA analysis have shown a 1.7-fold increase in the CBS expression at 1 week post-injury, as compared to the intact trout. In the ventricular and subventricular regions of trout telencephalon, CBS+ cells, as well as neuroepithelial and glial types, were detected. As a result of injury, the number of CBS+ neuroepithelial cells in the pallial and subpallial periventricular regions of the telencephalon increases. In the tectum, a traumatic damage leads to an increase in the CBS expression in radial glia with a simultaneous decrease in the number of CBS immunopositive neuroepithelial cells detected in intact animals. In the cerebellum, we revealed neuroglial interrelations, in which H2S is probably released from the astrocyte-like cells with subsequent activation of the neuronal NMDA receptors. The organization of the H2S-producing cell complexes suggests that the amount of glutamate produced in the trout cerebellum and its reuptake is controlled with the involvement of astrocyte-like cells, reducing its excitotoxicity. We believe that the increase in the number of H2S-producing cells constitutes a response to oxidative stress, and the overproduction of H2S neutralizes the reactive oxygen species.
研究了眼损伤1周后鳟鱼端脑、顶盖和小脑中产生h2s的系统。ELISA分析结果显示,与完整的鳟鱼相比,CBS在损伤后1周的表达增加了1.7倍。在鳟鱼端脑的脑室和脑室下区,检测到CBS+细胞,以及神经上皮和胶质类型。损伤后,端脑侧和侧下侧脑室周围区域的CBS+神经上皮细胞数量增加。在顶盖中,创伤性损伤导致放射状胶质细胞中CBS表达增加,同时在完整动物中检测到的CBS免疫阳性神经上皮细胞数量减少。在小脑中,我们发现了神经胶质的相互关系,其中H2S可能从星形细胞样细胞释放,随后激活神经元NMDA受体。产生h2s的细胞复合体的组织表明,鳟鱼小脑中谷氨酸的产生及其再摄取受星形细胞样细胞的参与控制,从而降低了其兴奋毒性。我们认为,产生H2S的细胞数量的增加是对氧化应激的反应,过量产生H2S可以中和活性氧。
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引用次数: 1
Aptamers and Possible Effects on Neurodegeneration 适体及其对神经退行性变的可能影响
Pub Date : 2019-11-26 DOI: 10.5772/INTECHOPEN.89621
F. Söylemez, Çağatay Han Türkseven
Aptamers are a new class of recognizing agents which are defined as short biomolecules like oligonucleotides and peptides that are used in diagnostics and therapeutics. They can bind to specific targets with extremely high affinity based on their structural conformations. It is believed that in the near future, aptamers could replace monoclonal antibody. The biggest advantage of using aptamers is that the process is in vitro in nature and does not require the use of animals and they also have unique properties, such as thermal stability, low cost, and unlimited applications. Aptamers have been studied as a biomaterial in numerous investigations concerning their use as a diagnostic and therapeutic tool and biosensing probe. DNA aptamers were also used for the diagnosis and treatment of neurodegeneration and neurodegenerative diseases. For example, functional nucleic acid aptamers have been developed to detect Aβ fragments in Alzheimer’s brain hippocampus tissue samples. Aptamers are promising materials for diverse areas, not just as alternatives to antibodies but as the core components of medical equipment. Although they are in the preliminary stages of development, results are quite encouraging, and it seems that aptamer research has a very bright future in neuroscience.
适配体是一类新型的识别因子,被定义为短生物分子,如寡核苷酸和多肽,用于诊断和治疗。根据它们的结构构象,它们可以以极高的亲和力与特定的目标结合。相信在不久的将来,适体可以取代单克隆抗体。使用适配体的最大优点是该过程是在体外进行的,不需要使用动物,而且它们还具有独特的性能,如热稳定性、低成本和无限的应用。适体作为一种生物材料在许多研究中被用作诊断和治疗工具和生物传感探针。DNA适体也被用于神经退行性疾病的诊断和治疗。例如,已经开发出功能性核酸适体来检测阿尔茨海默病大脑海马组织样本中的Aβ片段。适配体在许多领域都是很有前途的材料,不仅可以作为抗体的替代品,还可以作为医疗设备的核心部件。虽然它们还处于发展的初级阶段,但结果是相当令人鼓舞的,似乎适体研究在神经科学领域有着非常光明的前景。
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引用次数: 3
Polyphenols as Potential Therapeutic Drugs in Neurodegeneration 多酚作为神经退行性疾病的潜在治疗药物
Pub Date : 2019-10-23 DOI: 10.5772/intechopen.89575
P. P. Laureto, L. Palazzi, L. Acquasaliente
Several therapeutic approaches have been suggested so far for the treatment of neurodegenerative diseases, but to date, there are no approved therapies. The available ones are only symptomatic; they are employed to mitigate the disease manifestations and to improve the patient life quality. These diseases are characterized by the accumulation and aggregation of misfolded proteins in the nervous system, with different specific hallmarks. The onset mechanisms are not completely elucidated. Some promising approaches are focused on the inhibition of the amyloid aggregation of the proteins involved in the etiopathology of the disease, such as Aβ peptide, Tau, and α-synuclein, or on the increase of their clearance in order to avoid their aberrant accumulation. Here, we summarize traditional and new therapeutic approaches proposed for Alzheimer’s and Parkinson’s diseases and the recent technologies for brain delivery.
到目前为止,已经提出了几种治疗神经退行性疾病的方法,但到目前为止,还没有批准的治疗方法。现有的药物只是有症状的;他们被用来减轻疾病的表现和提高患者的生活质量。这些疾病的特点是神经系统中错误折叠蛋白的积累和聚集,具有不同的特异性标志。发病机制尚未完全阐明。一些有希望的方法集中在抑制与疾病病因有关的蛋白质的淀粉样蛋白聚集,如Aβ肽、Tau蛋白和α-突触核蛋白,或增加它们的清除以避免它们的异常积累。在这里,我们总结了阿尔茨海默病和帕金森病的传统和新的治疗方法以及最近的脑输送技术。
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引用次数: 3
期刊
Neuroprotection - New Approaches and Prospects
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