白藜芦醇治疗阿尔茨海默病的研究进展

神经退行性疾病是一种慢性进展性疾病,其特点是中枢神经系统神经元的逐渐丧失。由于血脑屏障的存在,经典的抗炎药物如类固醇激素和非甾体类抗炎药,对神经系统疾病的治疗作用有限。因此,开发新的抗炎药物,对于预防和治疗神经系统疾病具有重要的意义。白藜芦醇是一种有很强活性的天然多酚类物质,目前研究已显示其具有心血管保护、神经保护、免疫调节、肿瘤的化学预防作用。近年来还发现其具有抗神经炎症作用,可用于治疗神经精神性疾病,如帕金森病、阿尔茨海默病(AD)和亨廷顿症等。综述白藜芦醇对AD的保护作用及其机制研究进展,为进一步推进白藜芦醇用于防治AD的研究提供参考。     

基于抑郁症病理机制探讨芦丁抗抑郁作用

芦丁是一种广泛存在于芸香、槐角、红旱莲等植物中的黄酮醇苷类成分,具有抗氧化、抗菌、抗炎、保护心脑血管等药理作用。目前研究已证明,芦丁可通过血脑屏障,作用于大脑改善认知障碍,对氧化应激、脑缺血所致的神经损伤发挥保护作用。抑郁症是一类精神障碍类疾病,主要症状为情绪低落、思维迟缓、认知功能受损等,严重影响着人类健康和生命安全。通过查阅中国知网、 PubMed 等数据库,本文将基于抑郁症的病理机制,从芦丁调控单胺类神经递质与脑源性神经营养因子水平,改善下丘脑-垂体-肾上腺轴功能,影响谷氨酸能、 GABA 能、胆碱能系统与肠道微生物群、炎症等方面进行文献梳理,探讨其潜在抗抑郁作用的研究进展,为深入研究芦丁治疗抑郁症提供思路与理论基础。     

植物雌激素对神经保护作用的研究进展

目的 阐明植物雌激素的主要生物学特性和神经保护作用.方法 阐述并探讨植物雌激素的化学结构、体内活性形式、生物学特性及其对中枢神经系统功能的影响和神经保护作用的可能机制.结果 植物雌激素具有拮抗Aβ的毒性作用、增强胆碱能种经细胞的表达、调控胺能神经以及调节氨基酸兴奋性的生物学特性,并能对神经系统起到保护作用.结论 植物雌激素为神经系统疾病的预防和治疗提供了新思路,有望成为雌激素的替代药物.     

黄芩苷抗脑缺血药理学研究进展

缺血性脑中风是高死亡率和高致残率的神经系统疾病之一,加强缺血性脑中风的预防和治疗迫在眉睫。黄芩苷是中药黄芩的主要有效成分,能够透过血脑屏障发挥神经保护作用,可用于缺血性脑中风的治疗。该文从抗氧化应激、抗凋亡、抗炎、抗兴奋性氨基酸毒性、抗凝血酶细胞毒性、调节脑源性神经营养因子表达、调节热休克蛋白70表达、保护血脑屏障、促进神经再生等方面,综述了黄芩苷对缺血性脑中风的神经保护作用及作用机制研究进展,为黄芩苷治疗缺血性脑中风的临床应用提供科学依据。     

锂盐在精神疾病中的应用

锂盐作为情绪稳定剂用于治疗双相情感障碍已有60多年的历史,大量研究证明锂盐用于治疗急性躁狂以及对预防双相情感障碍的反复发作有效。锂盐还具有独特的预防自杀风险的效应,可降低情感障碍患者的自杀风险。最近锂盐在神经精神方面的应用研究有了新的进展,其独特的机制更是在不同的领域中被发现并应用,锂盐通过作用于GSK-3的抑制来发挥神经保护作用,这种保护作用对神经退行性疾病阿尔茨海默病、帕金森病、亨廷顿病的防治具有潜在用途。几个旨在评估锂盐对这些疾病疗效的临床试验正在进行中。     

银杏叶提取物对神经退行性疾病的作用机制及研究进展

随着人口老龄化的加快,神经退行性疾病的发病率呈逐年上升的趋势。神经退行性疾病具有病因复杂、病程长、难治愈等特点,目前银杏叶提取物的神经保护作用已被广泛认可,但其有效成分及其具体作用机制尚未明确。本文将根据神经退行性疾病的发病机制来探讨银杏叶提取物对神经的保护作用,主要从其改善Aβ聚集、抗炎、抗氧化、抗凋亡、保护线粒体、调节能量代谢等角度来研究其治疗神经退行性疾病的机制。     

补阳还五汤治疗神经退行性疾病作用机制研究进展

神经退行性疾病是多基因、多因素综合作用结果的复杂性疾病,其机制非常复杂尚不完全明确,目前缺乏理想的治疗手段。针对此类复杂疾病,中医药以系统性、科学性、整体性为神经退行性疾病做出诊治,补阳还五汤出自清代医林改错,主治气虚血瘀相关症状,在临床上被广泛使用,现代药理研究发现,补阳还五汤有广泛的神经保护作用机制靶点,对神经退行性疾病有明显疗效。本文综述了神经退行性疾病的一些相关疾病,并就补阳还五汤对此类疾病中的作用机制及其相关强大神经保护作用展开综述,以期为神经退行性疾病新药研发提供思路。     

褪黑激素对神经元保护作用的研究现状

褪黑激素是由松果体分泌的一种吲哚类激素,具有多种神经保护功能,可通过抗氧化、抗凋亡等作用保护神经细胞。而神经系统疾病的发生与氧化损伤和细胞凋亡等密切相关。本文主要从褪黑激素对神经元的保护作用及其作用机制作一综述,为临床上褪黑激素应用于神经疾病的治疗提供了理论依据。     

人参皂苷Rg1的神经保护作用研究进展

人参皂苷Rg1是人参中最主要的皂苷成分之一,具有广泛的药理活性,被认为是一种强大的神经保护剂,具有抗神经炎症、抗氧化应激、抗神经凋亡和增强记忆力等神经保护作用。Rg1在防治阿尔茨海默症、帕金森病、脑卒中等神经退行性疾病及抑郁症等精神类疾病中展现出了良好的应用前景。本文就近些年国内外对Rg1的神经保护作用机制研究进行综述,旨在为临床上治疗神经系统性疾病提供新的研究思路。     

芦丁防晒霜的试制

目的 为预防紫外线对皮肤的晒伤提供一个安全有效的制剂。方法建立芦丁防晒霜的制备工艺、内控标准并检测其紫外吸收特性，探讨作用原理。结果芦丁防晒霜质量稳定，对紫外线有广谱吸收的作用。结论芦丁防晒霜具有广谱防晒的性能，值得推广和开发。     

中药治疗重大疾病的研究进展

本文概要介绍中药治疗恶性肿瘤、心（脑）血管疾病、阿尔茨海默病、糖尿病、抑郁症和病毒性肝炎等重大疾病的研究进展。     

Recent trends in the transdermal delivery of therapeutic agents used for the management of neurodegenerative diseases

With the increasing proportion of the global geriatric population, it becomes obvious that neurodegenerative diseases will become more widespread. From an epidemiological standpoint, it is necessary to develop new therapeutic agents for the management of Alzheimer’s disease, Parkinson’s disease, multiple sclerosis and other neurodegenerative disorders. An important approach in this regard involves the use of the transdermal route. With transdermal drug delivery systems (TDDS), it is possible to modulate the pharmacokinetic profiles of these medications and improve patient compliance. Transdermal drug delivery has also been shown to be useful for drugs with short half-life and low or unpredictable bioavailability. In this review, several transdermal drug delivery enhancement technologies are being discussed in relation to the delivery of medications used for the management of neurodegenerative disorders.     

Therapeutic strategy at the crossroad of neuroinflammation and oxidative stress in age-related neurodegenerative diseases

Aging is the greatest risk factor for neurodegenerative diseases in the CNS, including two major age-related neurodegenerative diseases, Alzheimer’s disease and Parkinson’s disease. Understanding the biology of aging is pivotal in management of patients with neurodegenerative disorders. Genetically programmed aging and oxidative stress-elicited aging are two mechanisms of aging that are likely intertwined, leading to neurodegenerative damages. It is a commonly accepted that neurodegenerative diseases are the consequences of overproduction of oxidative stress or a result of compromised antioxidative mechanisms regardless of their aetiology. In aged brain, microglia increase in number and switch to a more pro-inflammatory state, providing a basis for greater inflammatory responses to inflammogens. Unfortunately, these unfavorable changes are often coupled with compromised capacity to remove oxidative products, allowing mutual perpetuation of inflammation and oxidative damage. This review highlights roles of microglia-mediated neuroinflammation and oxidative stress and association of these two. The possible novel therapeutic approaches are discussed in the context of focusing only on those possessing anti-inflammatory or antioxidative properties.     

Neurotoxicity as a Mechanism for Neurodegenerative Disorders: Basic and Clinical Aspects

This three day meeting focused on chronic neurodegenerative diseases such as Parkinson’s disease (PD), Alzheimer’s disease (AD) and amylotrophic lateral sclerosis (ALS). It attracted 69 participants from 10 countries with dominance of Chile and USA. Neurodegeneration and its prevention increasingly gain in importance as the number of people affected increases year-by-year. The meeting addressed various basic aspects having pragmatic implications such as: oxidative stress, inflammatory reaction, glial activation, role of glutamatergic system and apoptosis using a plethora of in vitro and in vivo methods.     

Targeting glucose-dependent insulinotropic polypeptide receptor for neurodegenerative disorders

Introduction: Incretin hormones, glucose-dependent insulinotropic polypeptide (GIP), and glucagon-like peptide-1 (GLP-1) exert pleiotropic effects on endocrine pancreas and nervous system. Expression of GIP and GIP receptor (GIPR) in neurons, their roles in neurogenesis, synaptic plasticity, neurotransmission, and neuromodulation uniquely position GIPR for therapeutic applications in neurodegenerative disorders. GIP analogs acting as GIPR agonists attenuate neurobehavioral and neuropathological sequelae of neurodegenerative disorders in preclinical models, e.g. Alzheimer’s disease (AD), Parkinson’s disease (PD), and cerebrovascular disorders. Modulation of GIPR signaling offers an unprecedented approach for disease modification by arresting neuronal viability decline, enabling neuronal regeneration, and reducing neuroinflammation. Growth-promoting effects of GIP signaling and broad-based neuroprotection highlight the therapeutic potential of GIPR agonists.

Areas covered: This review focuses on the role of GIPR-mediated signaling in the central nervous system in neurophysiological and neuropathological conditions. In context of neurodegeneration, the article summarizes potential of targeting GIPR signaling for neurodegenerative conditions such as AD, PD, traumatic brain injury, and cerebrovascular disorders.

Expert opinion: GIPR represents a validated therapeutic target for neurodegenerative disorders. GIPR agonists impart symptomatic improvements, slowed neurodegeneration, and enhanced neuronal regenerative capacity in preclinical models. Modulation of GIPR signaling is potentially a viable therapeutic approach for disease modification in neurodegenerative disorders.     

Can statins put the brakes on Alzheimer’s disease?

Statins inhibit 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, which initiates the syntheses of cholesterol and isoprenoid lipids that are needed to provide amyloid peptides for the amyloid cascade. This cascade is believed to induce sporadic or late-onset Alzheimer’s disease, which accounts for 90 – 95% of Alzheimer’s disease sufferers. Cholesterol is also the prime driver of cerebrovascular disease that (along with amyloid peptides) increasingly appears to be linked to the cognitive deterioration of Alzheimer’s disease. Cholesterol is needed to make the lipid rafts that are the platforms for isoprenoid-dependent assembly and activation of raftophilic β- and γ-secretases that work in tandem to excise dangerous 40 and 42 amino acid amyloid-β (Aβ) fragments from amyloid precursor protein, the transmembrane amyloid precursor glycoprotein. When they are excessively produced and can no longer be effectively destroyed or otherwise cleared from the hypoperfused ageing brain, the Aβ42 fragments released from the active synaptic terminals of normally busy neurons (and from stressed neurons unsuccessfully trying to proliferate and producing disruptive tangles of hyperphosphorylated τ-proteins) aggregate into neuritic plaques, which activate glial cells. The pro-inflammatory cytokines and growth factors from the glial cells further damage and kill neurons. As statins strike at several parts of the Alzheimer’s disease mechanism (such as the infliction of cholesterol-dependent cerebrovascular damage) by inhibiting HMG-CoA reductase, their long-term use (starting as early as possible during Alzheimer’s disease development) should slow or even prevent the progression of Alzheimer’s disease. Indeed, there is some evidence of a significantly reduced incidence of Alzheimer’s disease among people who have been using statins to reduce hypercholesterolaemia and its cardiovascular effects. To be certain of this, there must be more multi-year trials to specifically assess the effects of statins on sporadic Alzheimer’s disease.     

The promise of crowdfunding to finance R&D of novel diagnostics and therapeutics for incurable diseases

The level of funding available for research and development (R&D) of diagnostics (D) and therapeutics (T) for incurable diseases varies and is not associated with the extent of their disease burden. Crowdfunding is a promising way to increase funding for R&D of D&T for underfunded incurable diseases, such as Alzheimer’s and Parkinson’s disease, which has not been exploited to its full capacity. Investing into efforts to educate patients and researchers about its prospective is a worthwhile endeavor, which could lead to the generation of substantial new capital to finance the development of novel therapeutics for these diseases.     

Targeting toll-like receptor 4 to modulate neuroinflammation in central nervous system disorders

ABSTRACT

Introduction: Adverse immune activation contributes to many central nervous system (CNS) disorders. All main CNS cell types express toll-like receptor 4 (TLR 4). This receptor is critical for a myriad of immune functions such as cytokine secretion and phagocytic activity of microglia; however, imbalances in TLR 4 activation can contribute to the progression of neurodegenerative diseases.

Areas covered: We considered available evidence implicating TLR 4 activation in the following CNS pathologies: Alzheimer’s disease, Parkinson’s disease, ischemic stroke, traumatic brain injury, multiple sclerosis, multiple systems atrophy, and Huntington’s disease. We reviewed studies reporting effects of TLR 4-specific antagonists and agonists in models of peripheral and CNS diseases from the perspective of possible future use of TLR 4 ligands in CNS disorders.

Expert opinion: TLR 4-specific antagonists could suppress neuroinflammation by reducing overproduction of inflammatory mediators; however, they may interfere with protein clearance mechanisms and myelination. Agonists that specifically activate myeloid differentiation primary-response protein 88 (MyD88)-independent pathway of TLR 4 signaling could facilitate beneficial glial phagocytic activity with limited activity as inducers of proinflammatory mediators. Deciphering the disease stage-specific involvement of TLR 4 in CNS pathologies is crucial for the future clinical development of TLR 4 agonists and antagonists.     

SMi 4th Annual Conference on Neurodegenerative Disorders: a focus on Alzheimer’s and Parkinson’s disease

This was a small (~ 50 people) focused meeting on neurodegenerative disorders, with most of the speakers being from biotechnology or major pharmaceutical companies. The meeting covered a range of topics including introductions to Alzheimer’s disease and Parkinson’s disease, examples of targeting particular receptors/pathways, animal models and preclinical studies, clinical trial design and the use of biomarkers and imaging modalities. The major focus in the Alzheimer’s disease area was finding symptomatic treatments that are superior to acetylcholinesterase inhibitors and the extensive efforts that are ongoing to develop disease-modifying therapies. In terms of Parkinson’s disease there are now several reports examining the effects of dopamine agonists versus 3,4-dihydroxyphenylalanine on disease progression, and ongoing work with growth factors (e.g., glial cell line-derived neurotrophic factor) and mixed lineage/c-Jun N-terminal kinase inhibitors, such as CEP-1347. Small molecules that enhance endogenous signalling and repair pathways were also discussed.     

Repurposing small-molecule drugs for modulating toxic protein aggregates in neurodegenerative diseases

Neurodegenerative diseases (NDs) are often age-related disorders that can cause dementia in people, usually over 65 years old, are still lacking effective therapies. Some NDs have recently been linked to toxic protein aggregates, for example Alzheimer’s disease, Parkinson’s disease, Amyotrophic lateral sclerosis and Huntington disease; therefore, mulating toxic protein aggregates would be a promising therapeutic strategy. Moreover, drug repurposing, in other words exploiting drugs that are already in use for another indication, has been attracting mounting attention for potential therapeutic purposes in NDs. Thus, in this review, we focus on summarizing a series of repurposed small-molecule drugs for eliminating or inhibiting toxic protein aggregates and further discuss their intricate molecular mechanisms to improve the current ND treatment. Taken together, these findings will shed new light on exploiting more repurposed small-molecule drugs targeting different types of toxic proteins to fight NDs in the future.