Rho GTP酶在神经退行性疾病中的研究进展

神经退行性疾病,如帕金森病(PD)、阿尔兹海默症(AD)和肌萎缩侧索硬化症(ALS)等是现代医学界待于攻克的一大类致死性疾病。迄今,该类疾病已被确定的病理机制包括轴突变性、蛋白质聚集和蛋白质功能障碍等。神经元与靶细胞之间形成正确的连接是神经系统发育的基本过程之一。通过轴突导向和神经活动之间的相互作用,可成功的实现神经连接,若连接失败则会引起神经紊乱,导致相关疾病的发生。Rho GTP酶是肌动蛋白细胞骨架的关键调节因子,在神经元极性的建立、突触的形成、轴突和树突的延伸、轴突导向等方面都发挥着至关重要的作用。Rho GTP酶可能参与多种神经退行性疾病进程,有望成为该类疾病治疗的分子靶点。     

褪黑素在神经退行性疾病中的应用

神经退行性疾病是一类由急慢性病理因素所引发的, 以神经细胞变性, 丢失、 退化为主要病理 特征的中枢神经系统功能衰退性疾病。 它是第二大类常见的死亡原因, 预防神经退行性疾病已成为一个新 兴的公共卫生领域, 对我们社会造成了巨大的挑战。 褪黑素是松果体激素, 具有多种生理功能, 主要包括 调节昼夜节律, 清除自由基, 抑制生物分子氧化, 抑制神经炎症。 神经退行性疾病患者褪黑素的水平降低, 褪黑素通过调节病理生理机制和信号通路发挥神经保护作用, 提示褪黑素有可能成为新的治疗药物。     

长链非编码RNA在神经退行性疾病中的研究进展

常见的神经退行性疾病有AD、PD、HD以及ALS等,是以神经系统神经元细胞丧失为特征的一类疾病。目前没有有效的治疗措施,严重威胁着人们的生命和健康。长链非编码RNA(lnc RNA)是近年来生物学领域的研究热点。越来越多的相关研究表明lnc RNA与AD、PD、HD、ALS等神经退行性疾病的发生发展有着十分密切的关系。本文将探讨近年来lnc RNA在常见神经退行性疾病中的研究进展,为神经退行性疾病的基因诊断和基因治疗提供理论基础。     

神经退行性疾病中的自噬与再生研究进展

神经退行性疾病是由于神经元纤维的缠结和神经元的丢失所致,而产生功能障碍的现象,神经干细胞(NSCs)的损伤和生成减少也会引起神经退行性疾病的产生。自噬可以降解受损的细胞和细胞器,自噬在NSCs的增殖和分化中起着重要作用。mTOR和Notch都可以通过调节自噬来控制NSCs的生成,抑制mTOR信号通过干扰自噬作用于年龄相关的神经退行性疾病,自噬的改变可以影响Notch信号对NSCs分化的影响,本文归纳总结了自噬与再生在神经退行性疾病中作用的研究进展。     

神经营养因子及其在神经退行性疾病中的作用

正神经营养因子(neurotrophic factor,NTF)对神经功能的调控具有重要作用。当神经元损伤或发生病变时,NTF是作为保护神经元存活和促进再生的必需因子,同时它们与神经系统疾病的发生发展及治疗的关系相当密切~([1-3])。神经退行性疾病(neurodegenerative disease,NDD)是一类大脑和脊髓     

昼夜节律因子在神经退行性疾病中作用的研究进展

随着人类寿命的增加以及人口老龄化程度的加深,神经退行性疾病发病率逐年升高,严重威胁着人类的健康。目前神经退行性疾病常常存在发病机制不清、有效治疗手段较少、发病进程不可逆等特征。而生理昼夜节律作为维持生物体日常生命活动以及体内稳态的重要调节因素,受昼夜节律因子的调节,其失调可导致神经退行性疾病相关致病蛋白的积累、诱导相关致病激素的异常分泌,进而加重疾病的发病进程。本文围绕阿尔茨海默症(AD)、帕金森症(PD)和亨廷顿舞蹈症(HD)等常见的神经退行性疾病,论述昼夜节律因子调控神经退行性疾病的研究进展,以期为相关疾病发病机制以及干预治疗提供新的视角。     

伴侣蛋白Mortalin与神经退行性疾病的研究进展

1993年,Wadhwa等[1]在小鼠胚胎成纤维细胞(mouse embryonic fibroblasts, MEF)中首次克隆出了Mortalin(mtHSP70/HSP75/Grp75/TRAP-1/PBP74),它是热休克蛋白70(heat-shock protein 70, HSP70)家族成员之一.研究表明,Mortalin参与了多种生理功能的调控,包括细胞存活、细胞增殖、压力应激、线粒体合成、细胞内转运等,并且可能在神经系统疾病中发挥作用.在此,本文就Mortalin的基本结构、生理功能以及与神经系统疾病尤其是神经退行性疾病的相关性作一个综述.     

胰岛素抵抗在神经退行性疾病中的作用*

Insulin resistance is a condition in which the cells fail to respond to the normal actions of insulin, acting as decreased glucose utilization, abnormal glucose tolerance and compensatory increased insulin concentration in the serum. Altered insulin-related indicator has been detected in neurodegenerative diseases. Recent studies indicate that insulin resistance is involved in the occurrence and development of neurodegenerative diseases, including Alzheimers disease, Parkinsons disease, Huntingtons disease, etc. This review summarizes the relationship between insulin resistance and neurodegenerative diseases.     

硫化氢对神经退行性疾病保护作用的研究进展

硫化氢(hydrogen sulfide,H2S)一直被认为是一种有毒气体.近年来,越来越多的研究显示H2S在哺乳动物体内可以调节及参与一定范围的生理和病理过程.H2S在中枢神经系统中扮演着重要的角色.H2S具有抗氧化应激、抗凋亡以及抗炎的作用,而这些生理学意义对研究防治包括阿尔茨海默病、帕金森氏病在内的神经退行性疾病有着重要的启示.     

Benefits of Tai Chi Quan on neurodegenerative diseases: A systematic review

BackgroundNeurodegenerative diseases have become an important concern with the accelerated aging process. Tai Chi Quan (TCQ) has positive benefits for brain health and chronic diseases. The aim of this study was to summarize the protective effects of TCQ for motor function, cognition, quality of life, and mood in patients with neurodegenerative diseases.MethodsA systematic search was conducted via PubMed database and the Web of Science core collection database until August 20, 2021. The available English systematic reviews, meta-analyses, and clinical trials were included. Two reviewers completed the screening and assessment process independently.ResultsA total of 28 studies on Parkinson's disease, 21 on cognitive impairment, and 9 on multiple sclerosis met the included criteria. The study found that TCQ remarkably improved general motor function and balance, and prevented falls for Parkinson's disease. TCQ significantly improved global cognitive function for cognitive impairment. TCQ was likely safe and beneficial for multiple sclerosis as result of heterogeneous outcomes and small samples.ConclusionTCQ exercise can effectively improve the motor function, global cognitive function, and falls in patients with neurodegenerative diseases. However, the positive effects of TCQ on the quality of life and mood of patients with neurodegenerative diseases need further evidence.     

F2-isoprostanes in Alzheimer and other neurodegenerative diseases

Increased free radical-mediated injury to brain is proposed to be an integral component of several neurodegenerative diseases, including Alzheimer's disease (AD). Lipid peroxidation is a major outcome of free radical- mediated injury to brain, where it directly damages membranes and generates a number of oxidized products. F2-Isoprostanes (F2-IsoPs), one group of lipid peroxidation products derived from arachidonic acid, are especially useful as in vivo biomarkers of lipid peroxidation. F2-IsoP concentration is selectively increased in diseased regions of brain from patients who died from advanced AD, where pathologic changes include amyloid beta (Abeta) amyloidogenesis, neurofibrillary tangle formation, and extensive neuron death. Interestingly, cerebral F2-IsoPs are not reproducibly elevated in aged mouse models of cerebral Abeta amyloidogenesis only. There is broad agreement that increased cerebrospinal fluid (CSF) levels of F2-IsoPs also are present in patients with early AD. Demonstrated applications of quantifying CSF F2-IsoPs have improved laboratory diagnostic accuracy of AD and objective assessment of antioxidant therapeutics. In contrast, quantification of F2-IsoPs in plasma and urine of AD patients has produced conflicting data. These results indicate that brain lipid peroxidation is a potential therapeutic target early in the course of AD, and that CSF F2-IsoPs may aid in the assessment of antioxidant experimental therapeutics and laboratory diagnosis of AD.     

脑老化与神经系统退变性疾病

一般认为正常人或健康的脑老化现象，脑的结构与功能已发生病变，与出现以个体行为和认知能力等异常为基本临床表现的神经系统退变性疾病是两个相互独立现象。但是，已有许多证据表明，二者具有相互重叠的临床和神经病理特征、相似的生化改变和病因与发病机制。因此，现在有人认为，脑老化可能是神经系统退变性疾病的最初级阶段，与疾病的发生有着相同的基础。对它的认识，可为神经系统退变性疾病的治疗提出新的思路。本文拟对此作一介绍。     

神经营养因子与神经元退行性变疾病

神经元退行性变疾病包括多种疾病,如常见的老年性痴呆（alzheimer’s disease,AD）和帕金森病（parkinson disease,PD）等。此类疾病的共同特点是进行性的神经元损伤。由于发病机制复杂,并涉及许多至今未知的因素,目前尚无有效的干预措施,故阐明神经元退行性变疾病的发生机制十分重要。神经营养因子（neurotrophic factors,NTFs）是一类调节神经系统发育、成熟和维持神经元功能的天然蛋白质,在神经系统的发生、发育、营养、存活及损伤后修复中起重要作用,是神经元存活和发挥功能的基础。因此,本文主要讨论NTFs与神经元退行性变疾病特别是AD和PD之间的关系。     

Concise review: toward stem cell-based therapies for retinal neurodegenerative diseases

Loss of sight due to irreversible retinal neurodegeneration imposes a significant disease burden on both patients and society. Glaucoma and age-related macular degeneration are the commonest neurodegenerative blinding diseases in the developed world, and both are becoming increasingly prevalent as populations age. Our heavy reliance on our sense of sight means that visual loss often severely restricts day-to-day life, making it difficult to function without additional support. Visual impairment also limits employment possibilities, adding to the economic burden. Current therapies for many degenerative retinopathies are limited in their efficacy, often treating the effects of disease rather than the underlying causes. Consequently, the development of novel adjunctive neuroprotective and neuroregenerative treatments are important goals. Evidence from animal models suggests that stem cells could be useful as part of novel new treatment strategies for eye disease. The accessibility of the eye and extensive repertoire of available surgical techniques may facilitate the translation of stem cell-based therapies, for example, via transplantation, to the retina more rapidly than to other parts of the central nervous system. This concise review will examine how cell therapies are being applied experimentally for neuroregenerative and neuroprotective treatment of currently incurable degenerative retinal diseases. Furthermore, recent progress toward clinical translation of such therapies will be highlighted.     

Correlation between C9ORF72 mutation and neurodegenerative diseases: A comprehensive review of the literature

Chromosome 9 open reading frame 72 (C9ORF72) encodes a 54-kDa protein with unknown function that is expressed at high levels in the central nervous system. The C9ORF72 hexanucleotide amplification is one of the most recently discovered repetitive amplification diseases related to neurodegeneration. Its association with amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD) spectrum diseases has been fully established, although a causative role for C9ORF72 in Alzheimer''s disease (AD) and Parkinson''s disease (PD) remains to be established. Therefore, in this article, we will review the evidence for C9ORF72 as a causative factor in neurodegenerative diseases, the underlying mechanisms, and the potential for targeting C9ORF72 as a strategy to alleviate neurodegenerative disease progression.     

Inflammation in neurodegenerative diseases

Summary Neurodegeneration, the slow and progressive dysfunction and loss of neurons and axons in the central nervous system, is the primary pathological feature of acute and chronic neurodegenerative conditions such as Alzheimer’s disease and Parkinson’s disease, neurotropic viral infections, stroke, paraneoplastic disorders, traumatic brain injury and multiple sclerosis. Despite different triggering events, a common feature is chronic immune activation, in particular of microglia, the resident macrophages of the central nervous system. Apart from the pathogenic role of immune responses, emerging evidence indicates that immune responses are also critical for neuroregeneration. Here, we review the impact of innate and adaptive immune responses on the central nervous system in autoimmune, viral and other neurodegenerative disorders, and discuss their contribution to either damage or repair. We also discuss potential therapies aimed at the immune responses within the central nervous system. A better understanding of the interaction between the immune and nervous systems will be crucial to either target pathogenic responses, or augment the beneficial effects of immune responses as a strategy to intervene in chronic neurodegenerative diseases.     

Biomarker-based dissection of neurodegenerative diseases

The diagnosis of neurodegenerative diseases within neurology and psychiatry are hampered by the difficulty in getting biopsies and thereby validating the diagnosis by pathological findings. Biomarkers for other types of disease have been readily adopted into the clinical practice where for instance troponins are standard tests when myocardial infarction is suspected. However, the use of biomarkers for neurodegeneration has not been fully incorporated into the clinical routine. With the development of cerebrospinal fluid (CSF) biomarkers that reflect pathological events within the central nervous system (CNS), important clinical diagnostic tools are becoming available. This review summarizes the most promising biomarker candidates that may be used to monitor different types of neurodegeneration and protein inclusions, as well as different types of metabolic changes, in living patients in relation to the clinical phenotype and disease progression over time. Our aim is to provide the reader with an updated lexicon on currently available biomarker candidates, how far they have come in development and how well they reflect pathogenic processes in different neurodegenerative diseases. Biomarkers for specific pathogenetic processes would also be valuable tools both to study disease pathogenesis directly in patients and to identify and monitor the effect of novel treatment strategies.