一氧化氮神经毒性作用与神经退行性疾病

一氧化氮 (NO)作为神经系统中一种重要的信使分子 ,具有“双面刀”效应 ,既有重要的生理功能 ,同时又表现出神经毒性 ,与老年性痴呆、帕金森病等神经退行性疾病的发生密切相关。以往的研究已证实NO引起的神经细胞损伤是神经退行性疾病的致病环节之一。本文就NO在神经退行性疾病中的作用及其机制作一概述。     

小胶质细胞在慢性神经退行性疾病中的作用研究进展

随着社会的老龄化,神经退行性疾病的发病率呈逐渐上升的趋势,其会带来巨大的生理痛苦和社会负担。近年来,小胶质细胞在神经退行性疾病中的作用越来越受到重视。本文就小胶质细胞的特性以及小胶质细胞在阿尔茨海默病和帕金森病发生发展过程中的激活、吞噬、炎性作用等方面进行了综述,阐述了目前小胶质细胞在神经退行性疾病中的主要研究机制。     

148一氧化氮神经毒性作用与神经退行性疾病

一氧化氮（NO）作为神经系统中一个重要的信使分子,具有“双面刀”效应,既有重要的生理功能,同时又表现出神经毒性,与老年性痴呆、帕金森病等神经退行性疾病的发生密切相关。以往的研究已证实NO引起的神经细胞损伤是神经退行性疾病的致病环节之一。本文就NO在神经退行性疾病中的作用及其机制作一概述。     

泛素羧基末端水解酶-1与神经退行性疾病

神经退行性疾病是威胁人类健康的杀手之一,但是对于发病的原因和机理我们还所知甚少,研究表明在神经退行性疾病中,泛素蛋白酶体的活性受到抑制.泛素羧基端水解酶UCH-L1作为神经元中特异性表达的、脑内可溶性蛋白中含量最丰富的蛋白之一,在神经退行性疾病,尤其是帕金森和老年痴呆症中发挥着重要的作用.本文主要论述UCH-L1的功能和在神经退行性疾病中发挥的作用.     

哺乳动物雷帕霉素靶蛋白与神经退行性疾病

哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)作为细胞代谢和生存的关键调节剂,调节细胞的增殖,存活和代谢。越来越多的研究表明,mTOR是神经退行性疾病的新型治疗靶点,mTOR对于神经元的存活、发育和分化至关重要。 然而,基于mTOR介导的神经退行性疾病影响的分子机制尚未完全了解。本文综述了mTOR信号通路与神经退行性疾病之间关系的研究进展,并进一步讨论了mTOR在神经退行性疾病中的潜在作用。     

绿茶多酚防治老年神经退行性疾病研究进展

老年神经退行性疾病如帕金森病和阿尔茨海默病等均为多病因的复杂性疾病,在临床上单一作用靶点的药物治疗效果有限。绿茶多酚以其清除自由基、鳌合金属离子和调节神经细胞内蛋白激酶通路等作用在老年神经退行性疾病的防治中具有很大的潜力,本文就近年来该方面的研究进展进行阐述。     

番茄红素防治神经退行性疾病的研究进展

番茄红素是一种广泛存在于番茄、西瓜、石榴等植物体内的天然色素,属于类胡萝卜素家族成员,具有抗氧化应激、诱导细胞间隙连接通讯、调控细胞增殖等生物学功能。近年来,大量研究证实,番茄红素在防治神经退行性疾病方面发挥积极作用,其机制与抑制氧化应激、维持线粒体功能、抗细胞凋亡等多靶点作用密切相关。本文概述了近几年国内外有关番茄红素在神经退行性疾病中预防和治疗方面的研究进展。     

RNA干扰在神经退行性疾病发病机制研究和治疗方面的进展

神经退行性疾病是一类适用于RNA干扰疗法的疾病,其发病机制的复杂性又使RNA干扰成为探讨其发病机制的有效工具。本文针对RNA干扰在神经退行性疾病发病机制研究和治疗方面的应用进展进行了综述。通过小RNA干扰技术,在神经退行性疾病的模式动物中找到一批RNA的基因,创建模式动物中RNA组数据库,发现或/和揭示与一些重要生命现象和神经退行性疾病相关的RNA,建立一些以RNA为靶标的预防和治疗技术。     

肠道菌群对神经退行性疾病影响的研究进展

神经退行性疾病严重影响老年生存质量。其病因尚不明确且没有有效的治疗手段。研究表明,胃肠道通过肠脑轴与中枢神经系统进行交流,肠道菌群失调往往引发为神经系统症状,说明神经性退行性疾病的发病受到肠道菌群的影响。我们通过肠道菌群对神经退行性疾病的影响的研究进展进行综述,为研究神经性退行性疾病的机制及其有效防治提供新视角。     

辅酶Q10在AD等神经退行性疾病上的研究进展

辅酶Q10（CoQ10）是线粒体呼吸链中必不可少的辅酶,是电子传递链中重要的递氢体,参与线粒体产生能量ATP。一些动物模型试验和临床试验的研究显示CoQ10抗氧化和清除自由基的功能使其可能对神经有保护作用,它作为膳食补充剂,近年来在神经退行性疾病治疗中表现出一定潜能。本文针对CoQ10的生理生化性质及在阿尔茨海默病（ AD）等神经退行性疾病上的应用进展做一综述。     

Clinical value of nutritional status in neurodegenerative diseases: What is its impact and how it affects disease progression and management?

Neurodegenerative diseases constitute a major problem of public health that is associated with an increased risk of mortality and poor quality of life. Malnutrition is considered as a major problem that worsens the prognosis of patients suffering from neurodegenerative diseases. In this aspect, the present review is aimed to critically collect and summarize all the available existing clinical data regarding the clinical impact of nutritional assessment in neurodegenerative diseases, highlighting on the crucial role of nutritional status in disease progression and management. According to the currently available clinical data, the nutritional status of patients seems to play a very important role in the development and progression of neurodegenerative diseases. A correct nutritional evaluation of neurodegenerative disease patients and a right nutrition intervention is essential in monitoring their disease.     

Neurodegenerative diseases: an overview of environmental risk factors

The population of the United States is aging, and an ever-increasing number of Americans are afflicted with neurodegenerative diseases. Because the pathogenesis of many of these diseases remains unknown, we must consider that environmental factors may play a causal role. This review provides an overview of the epidemiologic evidence for environmental etiologies for neurodegenerative diseases such as Alzheimer disease, Parkinson disease, parkinsonian syndromes (multiple system atrophy and progressive supranuclear palsy), and amyotrophic lateral sclerosis. Epidemiologic evidence for an association between environmental agents' exposure and neurodegenerative diseases is not conclusive. However, there are indications that there may be causal links, and the need for more research is obvious.     

帕金森疾病相关蛋白DJ-1与微管相关蛋白MAP8的关系初步研究

[目的]探讨PARK7/DJ-1的突变与帕金森病的关系。[方法]以免疫共沉淀和免疫荧光的实验方法首次对DJ-1与MAP8可能存在关系,DJ-1与MAP8在细胞中存在共定位的作用关系进行探讨。[结果]DJ-1是一种在哺乳动物组织中广泛分布的蛋白,它可以保护细胞对抗氧化应激损伤以及具有分子伴侣的功能。细胞骨架系统的异常和神经变性疾病的发生密切相关,多种微管相关蛋白的非正常聚集可以引起神经变性疾病。MAP8是一种微管相关蛋白,在神经元形态发生和神经轴突生长中具有重要作用。实验进一步证明DJ-1可以抑制MAP8的非正常聚集和内含体(inclu-sion body)的形成。[结论]帕金森病是一种常见的神经变性疾病,PARK7/DJ-1的突变可以引起早发性的帕金森症状。     

Cytochrome P450 Metabolism of Polyunsaturated Fatty Acids and Neurodegeneration

Due to the aging population in the world, neurodegenerative diseases have become a serious public health issue that greatly impacts patients’ quality of life and adds a huge economic burden. Even after decades of research, there is no effective curative treatment for neurodegenerative diseases. Polyunsaturated fatty acids (PUFAs) have become an emerging dietary medical intervention for health maintenance and treatment of diseases, including neurodegenerative diseases. Recent research demonstrated that the oxidized metabolites, particularly the cytochrome P450 (CYP) metabolites, of PUFAs are beneficial to several neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease; however, their mechanism(s) remains unclear. The endogenous levels of CYP metabolites are greatly affected by our diet, endogenous synthesis, and the downstream metabolism. While the activity of omega-3 (ω-3) CYP PUFA metabolites and omega-6 (ω-6) CYP PUFA metabolites largely overlap, the ω-3 CYP PUFA metabolites are more active in general. In this review, we will briefly summarize recent findings regarding the biosynthesis and metabolism of CYP PUFA metabolites. We will also discuss the potential mechanism(s) of CYP PUFA metabolites in neurodegeneration, which will ultimately improve our understanding of how PUFAs affect neurodegeneration and may identify potential drug targets for neurodegenerative diseases.     

HFE gene variants affect iron in the brain

Iron accumulation in the brain and increased oxidative stress are consistent observations in many neurodegenerative diseases. Thus, we have begun examination into gene mutations or allelic variants that could be associated with loss of iron homeostasis. One of the mechanisms leading to iron overload is a mutation in the HFE gene, which is involved in iron metabolism. The 2 most common HFE gene variants are C282Y (1.9%) and H63D (8.9%). The C282Y HFE variant is more commonly associated with hereditary hemochromatosis, which is an autosomal recessive disorder, characterized by iron overload in a number of systemic organs. The H63D HFE variant appears less frequently associated with hemochromatosis, but its role in the neurodegenerative diseases has received more attention. At the cellular level, the HFE mutant protein resulting from the H63D HFE gene variant is associated with iron dyshomeostasis, increased oxidative stress, glutamate release, tau phosphorylation, and alteration in inflammatory response, each of which is under investigation as a contributing factor to neurodegenerative diseases. Therefore, the HFE gene variants are proposed to be genetic modifiers or a risk factor for neurodegenerative diseases by establishing an enabling milieu for pathogenic agents. This review will discuss the current knowledge of the association of the HFE gene variants with neurodegenerative diseases: amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease, and ischemic stroke. Importantly, the data herein also begin to dispel the long-held view that the brain is protected from iron accumulation associated with the HFE mutations.     

Pharmacological effects of protocatechuic acid and its therapeutic potential in neurodegenerative diseases: Review on the basis of in vitro and in vivo studies in rodents and humans

Protocatechuic acid has very promising properties potentially useful in the inhibition of neurodegenerative diseases progression. It is the main metabolite of the complex polyphenolic compounds and is believed to be responsible for beneficial effects associated with consumption of the food products rich in polyphenols. Protocatechuic acid is present in the circulation significantly longer and at higher concentrations than parent compounds and easily crosses the blood brain barrier. The aim of the following paper is to provide an extensive and actual report on protocatechuic acid and its pharmacological potential in prevention and/or treatment of neurodegenerative diseases in humans based on existing data from both in vitro and in vivo studies. Experimental studies strongly support the role of protocatechuic acid in the prevention of neurodegenerative processes, including Alzheimer’s and Parkinson’s diseases, due to its favorable influence on processes underlying cognitive and behavioral impairment, namely accumulation of the β-amyloid plaques in brain tissues, hyperphosphorylation of tau protein in neurons, excessive formation of reactive oxygen species and neuroinflammation. There is a growing evidence that protocatechuic acid may become in the future efficacious and safe substance that protects against neurodegenerative disorders.     

Involvement of environmental mercury and lead in the etiology of neurodegenerative diseases

The incidence of neurodegenerative disease like Parkinson's disease and Alzheimer's disease (AD) increases dramatically with age; only a small percentage is directly related to familial forms. The etiology of the most abundant, sporadic forms is complex and multifactorial, involving both genetic and environmental factors. Several environmental pollutants have been associated with neurodegenerative disorders. The present article focuses on results obtained in experimental neurotoxicology studies that indicate a potential pathogenic role of lead and mercury in the development of neurodegenerative diseases. Both heavy metals have been shown to interfere with a multitude of intracellular targets, thereby contributing to several pathogenic processes typical of neurodegenerative disorders, including mitochondrial dysfunction, oxidative stress, deregulation of protein turnover, and brain inflammation. Exposure to heavy metals early in development can precondition the brain for developing a neurodegenerative disease later in life. Alternatively, heavy metals can exert their adverse effects through acute neurotoxicity or through slow accumulation during prolonged periods of life. The pro-oxidant effects of heavy metals can exacerbate the age-related increase in oxidative stress that is related to the decline of the antioxidant defense systems. Brain inflammatory reactions also generate oxidative stress. Chronic inflammation can contribute to the formation of the senile plaques that are typical for AD. In accord with this view, nonsteroidal anti-inflammatory drugs and antioxidants suppress early pathogenic processes leading to Alzheimer's disease, thus decreasing the risk of developing the disease. The effects of lead and mercury were also tested in aggregating brain-cell cultures of fetal rat telencephalon, a three-dimensional brain-cell culture system. The continuous application for 10 to 50 days of non-cytotoxic concentrations of heavy metals resulted in their accumulation in brain cells and the occurrence of delayed toxic effects. When applied at non-toxic concentrations, methylmercury, the most common environmental form of mercury, becomes neurotoxic under pro-oxidant conditions. Furthermore, lead and mercury induce glial cell reactivity, a hallmark of brain inflammation. Both mercury and lead increase the expression of the amyloid precursor protein; mercury also stimulates the formation of insoluble beta-amyloid, which plays a crucial role in the pathogenesis of AD and causes oxidative stress and neurotoxicity in vitro. Taken together, a considerable body of evidence suggests that the heavy metals lead and mercury contribute to the etiology of neurodegenerative diseases and emphasizes the importance of taking preventive measures in this regard.     

Spatially informed Bayesian neural network for neurodegenerative diseases classification

Magnetic resonance imaging (MRI) plays an increasingly important role in the diagnosis and prognosis of neurodegenerative diseases. One field of extensive clinical use of MRI is the accurate and automated classification of degenerative disorders. Most of current classification studies either do not mirror medical practice where patients may exhibit early stages of the disease, comorbidities, or atypical variants, or they are not able to produce probabilistic predictions nor account for uncertainty. Also, the spatial heterogeneity of the brain alterations caused by neurodegenerative processes is not usually considered, despite the spatial configuration of the neuronal loss is a characteristic hallmark for each disorder. In this article, we propose a classification technique that incorporates uncertainty and spatial information for distinguishing between healthy subjects and patients from four distinct neurodegenerative diseases: Alzheimer's disease, mild cognitive impairment, Parkinson's disease, and Multiple Sclerosis. We introduce a spatially informed Bayesian neural network (SBNN) that combines a three-dimensional neural network to extract neurodegeneration features from MRI, Bayesian inference to account for uncertainty in diagnosis, and a spatially informed MRI image using hidden Markov random fields to encode cerebral spatial information. The SBNN model demonstrates that classification accuracy increases up to 25% by including a spatially informed MRI scan. Furthermore, the SBNN provides a robust probabilistic diagnosis that resembles clinical decision-making and can account for the heterogeneous medical presentations of neurodegenerative disorders.