帕金森病致病的分子研究进展

帕金森病 (Parkinsonsdisease)的病理学特征是中脑黑质多巴胺神经元的进行性缺失 ,其病因至今不明。近年研究表明氧化应激、线粒体功能失调和泛素 蛋白酶体系统功能损害等分子事件介导了多巴胺能神经元坏死 ,在帕金森病病变过程中起重要作用。对这些分子事件的研究和阐述有可能为帕金森病的药物治疗提供新的思路和途径。     

PI3K/Akt/mTOR信号通路与帕金森病关系的研究进展

帕金森病(PD)也称为震颤麻痹,是中老年人常见的以锥体外系症状(静止性震颤、动作迟缓及减少、肌张力增高、姿势步态异常等)为表现的神经系统变性疾病。其病理改变主要是黑质致密部多巴胺能神经元变性、缺失。目前认为,PD的病因可能与遗传、环境因素、年龄、细胞凋亡、氧化应激、线粒体功能衰竭、钙超载、兴奋性氨基酸毒性等有关。而越来越多的研究证明其发生的根本原因是多巴胺神经元进行性凋亡[1]。磷脂肌     

休克血液动力学变化的一些现代概念

一、休克的现代概念及分类:休克过去常被用来泛指以低血压为特征的各种威胁生命的病理状态。近年来对休克的认识深入了一步。目前认为休克的本质是机体组织、器官,特别是生命攸关器官,血流灌注量的不足,即循环系统的功能不足以维持组织器官的正常功能,应该把休克看成有效循环血量锐减时,机体为维护其生命攸关器官能正常活动所必需的血流量而进行的一场错综复杂的斗争。循环系统功能的调节的主要环节如图1所示。休克按其原始发病环节的不同,可分为下列四类。     

多糖化合物抗肿瘤机制研究进展

多糖化合物作为天然生物效应调节剂，具有肯定的调节机体免疫功能的作用，其作用是多途径、多环节的，不仅能促进T细胞、B细胞、NK细胞和巨噬细胞等免疫细胞的功能，还能促进白介素－2（IL－2）、干扰素（IFN）、肿瘤坏死因子（TNF）等细胞因子的产生。本文就多糖提高机体免疫功能及抗肿瘤机制进行综述。     

增强认知功能:治疗药物成瘾的新途径

<正>药物成瘾是一种伴随着认知功能改变的慢性脑疾病,其临床特征表现为强迫性觅药行为,并在戒断期及之后很长时间内持续存在心理渴求。许多成瘾理论认为,抑制力或执行控制力缺失是成瘾的标志性特征,会导致持续的药物滥用行为且难以治疗[1-3]。大部分的滥用药物可能导致认知功能受损,尤其在注意力、工作记忆和反应抑制力等方面。研究发现,认知功能损伤会影响成瘾治疗效果,许多改善认知功能的药物如加兰他敏、莫达非尼、阿托西     

金刚烷胺治疗帕金森综合征的临床研究

帕金森综合征(parkinson disease,PD),又称震颤麻痹,由英国医生Jame Parkinson在1817年首先详细描述,是中老年人常见的运动障碍疾病,以黑质多巴胺能神经元变性缺失和路易小体形成为病理特征,临床表现为静止性震颤、运动迟缓、肌强直和姿势步态异常等。随着对PD研究的深入,其治疗药物也越来越多,金刚烷胺这一具有40年历史的老药是否仍有其应     

中国饮食环境下餐饮服务物质安全风险管理及其检验

目的 为餐饮服务提供科学合理的监管途径.方法 分析餐饮服务的供应链条和涉及环节的多样性.结果 作为食品供应链条的中下游环节,餐饮服务的食品安全问题一方面来自于种植、加工、运输及零售等环节的危害物质积累;另一方面其本身的环节多样性也为食品安全带来了新的潜在风险.餐饮服务作为具有人文特征的消费提供方式,其食品安全监管必须针对饮食特征、习惯、环境来综合建立管理及检验模式.结论 物质管理、过程管理及链条化管理作为3种可应用于餐饮服务食品安全监管的模式,各有特点,其中链条化管理更能为餐饮服务提供合理的监管途径.     

微电泳urocortinⅡ对大鼠纹状体神经元自发放电及DA、ACH能神经传递影响

帕金森病(Parkinsoncs disease, PD) 是常见的中枢神经系统退行性病变,其主要病理特征为黑质-纹状体多巴胺(dopamine, DA) 能神经元变性缺失,乙酰胆碱(acetylcholine, ACH)能过度兴奋[1].其常见的发病机制包括:兴奋毒性、细胞凋亡及氧化应激学说[1-2].有研究表明,新型神经肽(urocortin, UCN)具有神经元保护作用,可用于PD、阿尔采末病等疾病的治疗[3-4].UCN是一种40个氨基酸小分子神经肽,由下丘脑分泌后刺激垂体前叶细胞释放促肾上腺皮质激素和β-内啡肽.目前研究认为UCN 可能具有神经系统保护功能[5-6],然而,UCN对基底神经节神经元放电的影响及对其他神经递质间的相互协调作用,未见报道.     

动脉粥样硬化相关因素研究进展

动脉粥样硬化是多因素相关的慢性血管病变,是心脑血管事件发病的重要病因。年龄、氧化型低密度脂蛋白、吸烟、肥胖及糖耐量减低在动脉粥样硬化的始动及发展环节起着不同程度的促进作用;而功能正常的高密度脂蛋白则通过胆固醇逆向转运、抗氧化等方式发挥其保护功能。本文拟对近年国内外多因素与动脉粥样硬化相关性的研究进行综述。     

青年人单个磨牙缺失对咀嚼功能的影响

青年人单个磨牙缺失对咀嚼功能的影响３７１医院（河南新乡４５３０００）管志江刘振卿孙强朱雪华谭成柱王志勤本文旨在研究单个磨牙缺失后其咀嚼功能的丧失情况，为临床上修复提供理论依据。１．材料和方法：选择每个病例只缺失一个磨牙，且前牙及对侧牙周情况良好，咬牙...     

他汀类药物对于阿尔茨海默病的疗效

流行病学和药理学研究结果显示，胆固醇在阿尔茨海默病(Alzheimer’s disease．AD)的发生中起着重要作用，他汀类药物对于AD具有潜在的治疗作用，今后这类药物可能被用来治疗AD。本综述了目前他汀类药物对AD的研究报道，并对他汀类药物、胆固醇、AD之间的作用机制进行了探讨，为AD的治疗和他汀类药物的新应用提供参考。     

RNAi技术在阿尔采末病防治研究中的应用

阿尔采末病(Alzheimer′s disease,AD)是一种神经退行性疾病,目前已成为严重威胁老年人生活质量乃至生命的主要疾病之一。由于AD的发病机制并不清楚,因此给其治疗带来了很大困难,目前的治疗方法都只能部分改善症状,而不能逆转病理变化或阻止病情的发展。近年来RNAi技术在体内外抑制AD相关基因表达的成功,为AD的治疗提供了新的方法。该综述主要介绍了RNAi技术在AD中的应用。     

Research progress of TREM2 in Alzheimer disease

Alzheimer disease(AD)is a common neurodegenerative disease in the elderly,but nowadays the pathogenesis of AD is unclear.Myeloid cell 2 trigger receptor(TREM2)is one of the most famous and most common rare mutations in neurodegenerative disease research,and its functional site mutation can significantly increase the incidence of AD.In this paper,we summary the structure,localization,and function and related signaling pathways of TREM2,review the latest epidemiological findings of TREM2 associated with the pathogenesis of AD,and speculate on the possible role of TREM2 in the progression of this disease,as well as the expression of TREM2 and the role of soluble TREM2 in AD brain are further elucidated.Based on the potential protective effect of TREM2 in the pathogenesis of AD,Therefore,targeting TREM2 may provide new opportunities and a reference for AD treatment.As the TREM2 variant appears to be widely involved in neurodegenerative diseases,there is an urgent need to further study the function of TREM2 in the brain and to find its ligands involved in TREM2-mediated signaling transduction and its specific role in AD pathogenesis.     

Always around, never the same: pathways of amyloid beta induced neurodegeneration throughout the pathogenic cascade of Alzheimer's disease

There is an increasing amount of evidence showing the importance of intermediate aggregation species of amyloid beta (Abeta) in the pathogenic cascade of Alzheimer's disease (AD). Different Abeta assembly forms may mediate diverse toxic effects at different stages of the disease. Mouse models for AD suggest that intraneuronal accumulation of Abeta oligomers might be involved in AD pathogenesis at a very early stage of the disease. The detrimental effect of oligomeric Abeta on synaptic efficacy is suggested to be an early event in the pathogenic cascade. Also early neuronal responses as activation of the unfolded protein response are processes likely to be associated with the increased occurrence of oligomeric or low fibrillar Abeta in AD pathology. In later stages of AD pathology, the fibrillarity of Abeta increases, concomitantly with a neuroinflammatory response, followed by tau related neurofibrillary changes in end stage pathology. We will review recent findings in in vitro cell models, in vivo mouse models, and post mortem AD brain tissue in view of the effects of different Abeta peptide species on neurodegeneration during AD pathogenesis. Insight into the role of different Abeta species during AD pathogenesis is essential for the development of disease modifying drugs and therapeutical strategies.     

Cholesterol and apoe: a target for Alzheimer's disease therapeutics

Alzheimer's disease (AD) is a debilitating disease that affects many people. In order to reduce the number of people diagnosed with this disease, drug strategies need to be implemented that target early steps in disease pathogenesis. Elevated cholesterol levels and presence of the apolipoprotein E eta4 allele increase AD risk. How these two factors may contribute to AD pathogenesis and some therapeutic strategies for alleviating AD risk will be discussed.     

阿尔茨海默病的纳米疗法研究进展

阿尔茨海默病(alzheimer's disease,AD)是一种中枢神经退行性疾病,在社会人口老龄化日益加剧的今天,AD患病率不断上升,其严重程度足以干扰人类的日常生活,危害人类的健康.目前AD的发病机制尚不明确,没有有效的药物可以治愈AD.血脑屏障(Blood brain barrier,BBB)是血液循环与中枢神经系统之间的生物屏障,药物不能穿过BBB,使其在治疗中枢神经系统疾病时有一定的局限性.纳米释药系统可以非侵入性地将药物递送至大脑,通过靶向药物递送,可以降低药物的毒性,增加药物的生物利用度.本文简述了AD发病的几种假说,介绍了与AD相关的纳米药物(Nanomedicines,NMs)种类和研究进展,对纳米递药技术在AD治疗策略中的应用进行阐述和列举,为AD的NMs研究提供思路和参考.     

Transgenic mouse models of Alzheimer's disease: phenotype and application

Alzheimer's disease (AD) is the most common cause of senile dementia, for which there is presently no disease-based treatment. The identification of genetic factors contributing to this disease, and the intense investigation into the cell biology of amyloid precursor protein (APP) and, to some extent, tau, has led to the development of several transgenic mouse models of this disease. These mice show some of the characteristic AD pathology, such as an age-dependent formation of amyloid plaques consisting of Abeta peptides. However, they usually lack both the tau pathology, i.e. neurofibrillary tangle formation, and the neurodegeneration also associated with AD. Importantly, many of these transgenic lines develop age-dependent deficits in some relevant behavioural tests and thus provide an animal model not only for amyloidosis but also for the cognitive deficits of AD patients. Incorporation of additional disease genes may lead to models that show a more complete disease phenotype. This review attempts to summarize much of this work, and describes how the availability of these models should assist in the understanding of AD aetiology and the identification of effective treatments for this disease. The review also considers the role behavioural testing may have in future AD drug discovery research.     

Review of theoretical studies for prediction of neurodegenerative inhibitors

Alzheimer's disease (AD) is characterized by several pathologies, this disease is a neuropathological lesion in brain. Indeed, a wealth of evidence suggests that β-amyloid is central to the pathophysiology of AD and is likely to play an early role in this intractable neurodegenerative disorder. AD is the most prevalent form of dementia, and current indications show that twenty-nine million people live with AD worldwide, a figure expected rise exponentially over the coming decades. Clearly, blocking disease progression or, in the best-case scenario, preventing AD altogether would be of benefit in both social and economic terms. However, current AD therapies are merely palliative and only temporarily slow cognitive decline, and treatments that address the underlying pathologic mechanisms of AD are completely lacking. While familial AD (FAD) is caused by autosomal dominant mutations in either amyloid precursor protein (APP) or the presenilin (PS1, PS2) genes. First, we revised 2D QSAR, 3D QSAR, CoMFA, CoMSIA and Docking of β and γ-secretase inhibitors. Next, we review 2D QSAR, 3D QSAR, CoMFA, CoMSIA and docking for GSK-3α and GSK-3β with different compound to find out the structural requirements.     

阿尔茨海默病:与性别、癌症、饮食有关吗?

阿尔茨海默病(AD)是一种以进行性记忆和认知障碍为主要临床特征的慢性神经退行性疾病,其发病原因尚不清楚。研究显示,AD与性别有关,其发病率女性明显高于男性,接受雄激素剥夺疗法的前列腺癌患者AD发病率也明显增高。此外,研究发现,AD与癌症呈负相关,癌症患者的记忆力要好于非癌症志愿者,AD患者患肿瘤的概率明显偏低。AD与饮食也呈一定的相关性,糖尿病患者的AD风险成倍增加引发人们对高碳饮食的担忧;地中海饮食、适度饮酒(红葡萄酒)和咖啡以及调节肠道菌群等均有利于预防AD,但仍需进一步研究。总之,AD是一种多因素疾病,其防治要“多管齐下”,运用多种防治策略才可能奏效。     

Therapeutic opportunities in Alzheimer disease: one for all or all for one?

In recent years, Alzheimer disease (AD) has received great attention as an incurable and fatal disease that threatens the lives of aging individuals. Debates regarding areas of research and treatment designs have made headlines as scientists in the field question ongoing work. Despite these academic quarrels, significant insights concerning the cellular and molecular basis of AD have illuminated the potential causes and consequences of AD pathogenesis in the human brain. Additionally, assigning relationships among scientific evidence is difficult due to the nature of the disease. It is crucial to note that all findings do not constitute causality as AD has many stages of progression, and therefore a particular finding may reflect disease epiphenomenon. Determining the primary causes of disease are even more problematic when considering that a succinct timeline in which a normal aging brain develops AD-like changes due to a single cause may not be appropriate, as increasing lines of evidence indicate that multiple factors likely contribute to the clinical manifestation of AD. Implications for therapeutic strategies are dramatically affected by viewing AD as a multi-factorial disease state, one specific treatment may not be able to prevent or reverse AD if this is indeed the case. In this regard, the current focus on individual therapeutic targets may prove to be ineffective in the successful treatment of AD; however, if taken in combination, these singular therapies may likely result in the global suppression of AD. In this review, the scientific basis for common AD therapeutics as well as the efficacy of these treatments will be discussed.