Synucleins: Are they two‐edged swords?

The synuclein family consists of three distinct highly homologous genes, α‐synuclein, β‐synuclein, and γ‐synuclein, which have so far been found only in vertebrates. Proteins encoded by these genes are characterized by an acidic C‐terminal region and five or six imperfect repeat motifs (KTKEGV) distributed throughout the highly conserved N‐terminal region. Numerous data demonstrate that synucleins are implicated in two groups of the most devastating human disorders, i.e., neurodegenerative diseases (NDDs) and cancer. Mutations in the α‐synuclein gene are associated with familial forms of Parkinson's disease (PD), and accumulation of α‐synuclein inclusions is a hallmark of this disorder. In breast cancer, increased expression of γ‐synuclein correlates with disease progression. Conversely, some results indicate that the members of the synuclein family may have a protective effect. How might these small proteins combine such controversial properties? We present evidence that synuclein's features are basically regulated by two mechanisms, i.e., posttranslational modifications (PTMs) and the level of their expression. We also discuss a new, emerging area of investigation of synucleins, namely, their role in the cell‐to‐cell propagation of pathology. © 2012 Wiley Periodicals, Inc.     

Synucleins in ocular tissues.

Synucleins are small proteins associated with neurodegenerative diseases and some forms of cancer. Most studies of this group of proteins have been directed to the elucidation of their role in the brain and their connection to the formation of depositions in brain tissues. Here we describe the localization of different types of synucleins in ocular tissues. By Western blot analysis, all members of the synuclein family are found in the retina and optic nerve, where their relative ratio varies. The data on immunohistochemical staining show that different members of the synuclein family have different localizations in ocular tissues. Alpha-synucleins and beta-synucleins are present predominantly in the inner plexiform layer, whereas gamma-synuclein is in the nerve fiber layer. In transgenic mice overexpressing alpha-synuclein, a different pattern of localization depending on the promoter used for the expression was observed. In Alzheimer's disease patients, immunohistochemical staining for gamma-synuclein revealed the loss of immunoreactivity in the nerve fiber layer and the nerve fiber layer and the appearance of immunopositive cells in or near the outer nuclear layer. We conclude that, in mature eyes, synucleins are present predominantly in the retina and optic nerve, and the immunoreactivity of gamma-synuclein changes specifically in the retina of Alzheimer's disease patients. In transgenic mice overexpressing alpha-synuclein, immunopositive deposits in the optic nerve and accumulation of immunoreactivity in specific retinal cells were found.     

胃癌组织SNCG和MAP2表达及临床意义

目的 探讨γ突触核蛋白(SNCG)和微管相关蛋白2(MAP2)在胃癌组织中的表达及其临床意义.方法 采用免疫组化方法检测90例胃癌及40例非肿瘤胃黏膜组织中SNCG和MAP2的表达.结果 胃癌组织SNCG和MAP2的阳性表达均显著高于非肿瘤胃黏膜组织(uc=7.149、7.100,P＜0.01);胃癌组织SNCG阳性表...     

胃癌组织SNCG和MAP2表达及临床意义

目的探讨γ突触核蛋白（SNCG）和微管相关蛋白2（MAP2）在胃癌组织中的表达及其临床意义。方法采用免疫组化方法检测90例胃癌及40例非肿瘤胃黏膜组织中SNCG和MAP2的表达。结果胃癌组织SNCG和MAP2的阳性表达均显著高于非肿瘤胃黏膜组织（uc=7.149、7.100,P〈0.01）;胃癌组织SNCG阳性表达与肿瘤浸润深度及淋巴结转移有关（uc=2.742、3.970,P〈0.05）,与性别、年龄以及分化程度无关（P〉0.05）;胃癌组织MAP2的阳性表达与肿瘤浸润深度及淋巴结转移有关（uc=2.382、4.363,P〈0.05）,与性别、年龄以及分化程度无关（P〉0.05）;胃癌组织中SNCG和MAP2的表达呈正相关（r=0.620,P〈0.05）。结论 SNCG和MAP2在胃癌的发生、发展及浸润转移中发挥着重要作用。     

Immunolocalization of alpha-synuclein in the rat spinal cord by two novel monoclonal antibodies

This study provides the first immunohistochemical evidence of the presence and distribution patterns in the rat spinal cord of α-synuclein (α-Syn), a soluble acidic protein, widely expressed in the CNS and closely associated to the pathogenesis of neurodegenerative conditions such as Parkinson's and Alzheimer's diseases. We used two novel homemade monoclonal antibodies (2E3 and 3D5) recognizing two different epitopes of α-Syn. Both antibodies localized α-Syn within the nerve terminals, whereas 3D5 alone also localized it within the neuronal nuclei. α-Syn-immunoreactive nervous elements were widely recognized throughout rat spinal cord and in almost all the gray matter laminae. However, they appeared particularly concentrated within laminae I, II, VII and X and more scattered in the others. Double immunofluorescent labeling showed that α-Syn colocalized with synaptophysin in the presynaptic nerve terminals, with neuropeptide Y (NPY) in lamina I, II, IX and X, and had close relationships with tyrosine hydroxylase (TH) immunoreactive neurons in laminae VII and X. Interestingly, the α-Syn-immunoreactive nerve elements, in lamina X, contained little of calbindin-28KD and calretinin-31KD. Our findings could help in understanding the genesis of some early clinical symptoms of Parkinson's disease (PD), such as pain and dysautonomic disorders, and indicate the spinal cord as their probable starting point, according to the ascending theory of PD, proposed by Braak.     

快速眼动睡眠行为障碍严重程度量表在特发性快速眼动睡眠行为障碍中的应用

目的探讨应用快速眼动睡眠行为障碍(RBD)严重程度量表(RBDSS)评价特发性RBD(iRBD)患者症状特点的异质性。方法选取iRBD患者118例,根据RBDSS评分分为亚临床RBD组(亚临床组)26例和症状性RBD组(症状组)92例。行视频-多导睡眠仪监测以及RBDSS评分并进行分析。结果症状组中伴有典型近端肢体活动及声音表现47例,占39.8%,远端肢体活动及声音表现为28例,占23.7%,轴向运动及声音表现为17例,占14.4%;亚临床组26例,占22.0%,差异有统计学意义(P<0.01)。2组各项睡眠参数比较,差异无统计学意义(P>0.05)。结论应用RBDSS可以评估iRBD患者的症状特点,并根据iRBD患者症状特点,采取不同的临床保护措施以及制定个体化治疗方案。