细胞转分化在神经系统疾病治疗中的研究进展

转分化是指在特定条件下,一种细胞转变为另一谱系细胞类型的过程。近年来,转分化技术在干细胞和再生医学领域迅速发展,为神经系统疾病的治疗带来曙光。目前,转分化技术在神经系统疾病治疗中的研究已涵盖了神经退行性疾病、创伤性神经系统损伤以及神经精神障碍疾病等多个疾病多种神经元亚型。利用丰富且易于获取的体细胞转分化得到难以再生的功能性神经元是再生医学的新思路。本文着重对目前转分化在神经系统疾病中的研究进行综述。     

神经退行性疾病发病机制的研究进展

正神经退行性疾病(Neurodegenerative diseases)是以发作迟缓和选择性神经元的功能障碍为特征表现,由于大脑和脊髓的神经元细胞丧失而引起的一类不可逆转的神经系统疾病,主要包括阿尔茨海默病(Alzheimer disease,AD)、帕金森氏病(Parkinson’s disease,PD)和亨廷顿氏病(Huntington’s disease,HD)等[1]。这些疾病临床表现均为认知功能下降,虽然其具有不同的组织病理学     

嘌呤受体在神经元和神经胶质细胞间信息传递中的作用

神经系统的功能在很大程度上取决于神经元-神经胶质细胞间的信息交流。而神经元与神经胶质细胞间复杂的信号通路间的相互作用涉及多种信号分子,嘌呤和嘌呤受体在此过程中起着重要作用。长久以来,关于中枢神经系统的研究主要集中在神经元,相比之下神经胶质细胞主要被作为支持细胞或在应对脑损伤时提供导向作用。最新研究表明,神经胶质细胞在神经系统疾病的发生发展中也扮演着重要角色。该文主要阐述嘌呤受体在神经元和神经胶质细胞之间的相互作用及其在神经系统疾病中的作用。     

自噬/溶酶体途径在帕金森病发生发展中的角色

帕金森病是一种以黑质纹状体区多巴胺能神经元进行性缺失和纹状体多巴胺含量显著减少为特征的中枢神经系统变性疾病.近年来,蛋白质的降解障碍被认为是帕金森病发病过程中的重要因素,自噬辕溶酶体途径是细胞内一种重要的蛋白降解途径,负责胞内泛素原蛋白酶体系统未能降解的大分子物质.自噬功能的失调和神经元的退行有重要的联系,自噬在清除与...     

P-糖蛋白在神经退行性疾病中的作用

神经退行性疾病( neurodegenerative disease)是一种以神经元退行性病变为基础的慢性进行性神经系统疾病,发病机制尚不明了,但一些内源性和外源性物质在脑部的异常聚集和沉积与其病因密切相关,且其往往是P糖蛋白的底物.近年来研究表明血脑屏障的p-糖蛋白在一些神经退行性疾病发展过程中表达会减少,这可能导致致病性内外源性物质的进一步聚集和沉积,恶化病情.本文对近年来有关P-糖蛋白在神经退行性疾病的发病和病情进展中的作用作一综述.     

以α-synuclein为靶点的抗帕金森病药物研究进展

帕金森病(Parkinsons disease,PD)是常见的神经退行性疾病,目前对PD的药物治疗仅限于改善症状,尚缺乏能够延缓疾病进程并具有神经保护作用的药物。α-突触核蛋白(α-synuclein,α-syn)是一种位于神经元突触前末端、由140个氨基酸组成的蛋白质,它的突变、聚集和过度积累与包括PD在内的一系列神经退行性疾病密切相关。开发针对α-syn及其相关靶点的药物,可能是控制PD等突触核蛋白病进程的有效途径。该文主要从抑制α-syn表达和聚集、促进其解聚和降解、调节其修饰状态等方面,对以α-syn为靶点的药物研究进展进行综述。     

小胶质细胞表达的受体与阿尔采末病

阿尔采末病(Alzheimer's disease,AD)是一种老年神经退行性疾病,其病因十分复杂,其中β-淀粉样蛋白(Aβ)毒性学说、tau蛋白过度磷酸化学说、基因突变、中枢胆碱能损伤学说等已得到普遍认可。近年来,由小胶质细胞介导的炎症学说也越来越受到重视。小胶质细胞是脑内先天性免疫反应的主要部位,在外源因子的刺激下可以表达大量受体,如TLRs、NLRs、RAGE等,这些受体在AD的发展过程中起重要作用。该文就由小胶质细胞激活所表达的受体与阿尔采末病的关系做一综述。     

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.     

小胶质细胞活化介导的神经元损伤与抑郁症的研究进展

抑郁症是一种常见的神经障碍,其发病率高,复发性高,致残性高,但发病机制未明。近年来,胶质细胞对神经元的保护与攻击作用已成为神经疾病研究的前沿方向。小胶质细胞(microglia, MG)异常活化导致神经元损伤在抑郁症发病中具有重要作用,该文通过GeenMedical、CNKI等进行文献检索,对MG活化相关通路及关键靶标在抑郁症中的研究进行归纳总结,为进一步的临床研究提供理论性的依据。     

胶质细胞介导的神经突触修剪在阿尔茨海默病中的作用

阿尔茨海默病(Alzheimer's disease,AD)是一种以记忆丧失、认知障碍为主要特征的神经退行性疾病,迄今尚无有效的治疗策略.神经突触是大脑神经元之间联系的部位,是产生记忆及其他神经活动的关键组成部分,神经突触的丢失是AD的重要病理特征.胶质细胞是大脑中除神经元以外的一类至关重要的细胞,其中最主要的两类胶质...     

Oxidative stress in human diseases

Oxidative stress is an abnormal phenomenon occurring inside our cells or tissues when production of oxygen radicals exceeds their antioxidant capacity. Excess of free radicals damage essential macromolecules of the cell, leading to abnormal gene expression, disturbance in receptor activity, proliferation or cell dye, immunity perturbation, mutagenesis, protein or lipofushin deposition. Numerous human diseases involve during the pathological process such a stress, localized or general (in the same way as inflammation). In many serious diseases such as cancer, ocular degeneration (age related macular degeneration or cataract), neurodegenerative diseases (ataxia, amyotrophic lateral sclerosis, Alzheimer's disease) stress is the factor original. In familial amyotrophic lateral sclerosis the genetic abnormality occurred an abnormal coding for an antioxidant enzyme, copper-zinc super oxide dismutase. In various other diseases oxidative stress occur secondary to the initial disease but plays an important in role immune or vascular complications. This is the case in infectious disease such as AIDS or septic shock, Parkinson's disease or renal failure. So antioxidant treatment seems logical to be tested in these pathologies. But they have to be applied early in the process, before irreversible mechanisms. They need also to be prescribed at low doses as baseline free radical production have to be preserved to maintain useful activity that cannot be suppressed.     

以G蛋白偶联受体为靶标的自身免疫性疾病的治疗（英文）

Our group is interested in the biological functions of G protein-coupled receptor(GPCR)and their roles in major diseases including autoimmune disease,neurodegenerative diseases,metabolic diseases,etc.In addition to the mechanism study,we also screen and develop drugs targeting GPCRs.In recent years,we also seek to study the mechanism of fate determination of stem cells with small molecule compounds.One of the autoimmune diseases we′re particularly interested is Multiple Sclerosis(MS).MS is an inflammatory disease that is characterized by immune-mediated demyelination and degeneration of the central nervous system.In the past few years,we′ve discovered that two GPCRs(CysLT1 and A2B)are critically involved in the development of MS by regulating the differentiation or function of immune cells.Blocking these receptors alleviates clinical symptoms of EAE,a mouse model of MS,indicating these receptors are potential drug targets for MS.Current drugs for MS all targets immune system.Although effective in reducing the relapse rate and the formation of new lesions,these drugs have very limited effects in preventing the progression of disability.Promoting oligodendrocyte progenitor cell differentiation,remyelination and subsequent functional recovery of the neurons have been proposed to be the new direction of MS therapy.Our recent study demonstrated that KOR,an opioid receptor,is important for oligodendrocyte-mediated remyelination in EAE,suggesting KOR might be a target to develop new MS therapies from a regenerative point of view.     

脑血管源性细胞间通讯异常与脑疾病机制研究

以脑卒中、阿尔茨海默病、癫痫等为主要代表的脑部疾病一直是危害人类健康的世界性难题,加重社会医疗负担。近年来,脑内神经血管单元不同类型细胞组分(脑血管内皮细胞、小胶质细胞、星形胶质细胞和神经元细胞)的联系与脑疾病之间的关系也越来越受到重视。在不同脑部疾病发生、发展及转归病理过程中,它们结构本身和通讯耦联功能产生着相应的变化。该综述在总结前人对细胞间通讯异常以及其与脑部疾病发作机制的相关研究的基础上,对其分子机制进行论述,以期找到治疗神经精神疾病的新靶点或新方法。     

Photosensitisers for the photodynamic therapy of cancer and other diseases

Photodynamic therapy is a relatively recent addition to the clinic, primarily for the treatment of cancer but also for psoriasis, age-related macular degeneration and other diseases. Photodynamic therapy utilises a photosensitiser that targets the disease site to produce a photochemical reaction following delivery of light. The properties of the photosensitiser are critical to the outcome of the technique and numerous classes have been developed in the past decade, including porphyrins and related compounds, chlorins, phthalocyanines, naphthalocyanines, texaphyrins, core-modified porphyrins and various cationic dyes. The potential of this technique is apparent from the extensive number of patents that have been awarded over the past three years.     

非结核分枝杆菌病的治疗研究进展

非结核分枝杆菌病系由结核分枝杆菌复合群和麻风分枝杆菌以外的分枝杆菌(Non-tuberculous mycobacteria,NTM) 引起的疾病。NTM除引起肺部病变外,尚可引起其他部位病变,常见的是淋巴结炎、皮肤软组织感染和骨骼系统病变,对严重的细胞免疫抑制者还可引起血源性播散。由于多数传统抗结核药物对大多数NTM很少或没有活性,所以NTM病治疗困难,预后不佳。近十余年来对NTM病的研究已取得很大进展,药物研究亦在迅速进展中。在原有抗结核药物的基础上,又出现了一些抗结核新药,其中一些对NTM病有效。尤其近年研究的疏水衍生物,显示了更大的抗NTM活性。     

气道黏液调节剂的药理作用

对近年来气道黏液调节剂的药理研究进展作一概述。在慢性呼吸道炎症疾病过程中，气道分泌细胞增生肥大、黏液分泌亢进，形成气道黏液高分泌。它已成为影响慢性阻塞性肺疾患病情和预后的独立危险因素。气道黏液调节剂能够抑制黏蛋白的产生及分泌，对气道黏液高分泌有治疗作用。     

Neuroprotection by caspase inhibitors

In the majority of brain diseases, apoptosis causes or exacerbates neuronal damage. Caspases are the final executioners of the apoptotic cell death programme. This family of proteases is implicated in the pathogenesis of many forms of brain damage, including those induced by ischaemia, inflammation or trauma, as well as those arising in Alzheimer's disease, Huntington's disease, amyotrophic lateral sclerosis and epilepsy. Collectively, these conditions affect more than 10 million people in the USA alone. Apoptosis can be blocked by agents that inhibit caspase activity; these inhibitors have therapeutic benefit in the treatment of several model systems of brain diseases. In this review we focus on recent advances and summarise current knowledge concerning the use of these cell death inhibitors in neuroprotection.     

Sphingosine kinase 1/sphingosine-1-phosphate receptors dependent signalling in neurodegenerative diseases. The promising target for neuroprotection in Parkinson’s disease

Parkinson’s disease (PD) is one of the most common serious neurodegenerative disorders in the world. The incidence of PD appears to be growing and this illness has an unknown pathogenesis. PD is characterized by selective loss of dopaminergic (DA) neurons in the substantia nigra (SN), with an enigmatic cause in most individuals. Current pharmacotherapies and surgery provide symptomatic relief but their effects against the progressive degeneration of neuronal cells are strongly limited if present at all. Therefore, uncovering novel molecular mechanisms of DA cell death and new potentially disease-modifying pharmacological targets is an important task for basic research. Significant progress has been made in understanding the role of disturbed sphingolipid metabolism, particularly relating to ceramide and sphingosine-1-phosphate (S1P) in the pathogenesis of Alzheimer's disease (AD) and other neurodegenerative diseases. Additionally, the neuroprotective potential of an S1P receptors (S1PR) modulator, fingolimod (FTY720), in multiple sclerosis (MS) and numerous other diseases has been observed over the past decade. In this review, we briefly summarise recent achievements in defining intracellular S1PR-dependent actions, discuss their significance to therapeutic approaches, and explore their neuroprotective potential as a target in PD treatment.     

神经干细胞移植治疗神经系统疾病的研究进展

神经系统疾病作为最大的医学挑战之一,目前尚无针对性的治疗方法。神经干细胞（NSCs）具有分化潜能,可通过组织修复替代、神经营养、免疫调节、抗炎、抗凋亡等达到治疗神经系统疾病的作用,为神经系统疾病的治疗提供了新思路。近年来针对NSCs的研究愈发深入,NSCs移植成为神经系统疾病治疗方法的研究热点,大量临床前及临床研究数据证明NSCs移植治疗用于神经系统疾病是安全可行的。目前已有多个NSCs细胞系进入临床试验阶段,有望用于脑卒中、脑出血、脊髓损伤、帕金森病、阿尔茨海默病等常见神经系统疾病的治疗。总结了NSCs移植治疗中枢神经系统疾病的研究进展,以期为NSCs移植治疗神经系统疾病研究提供理论支持。