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Synuclein migration

Dario Valdinocci, Gary Grant, Tracey Dickson, Dean L Pountney
Multiple System Atrophy (MSA) is a progressive neurodegenerative disease characterized by chronic neuroinflammation and widespread α-synuclein (α-syn) cytoplasmic inclusions. Neuroinflammation associated with microglial cells is typically located in brain regions with α-syn deposits. The potential link between microglial cell migration and the transport of pathological α-syn protein in MSA was investigated. Qualitative analysis via immunofluorescence of MSA cases (n = 4) revealed microglial cells bearing α-syn inclusions distal from oligodendrocytes bearing α-syn cytoplasmic inclusions, as well as close interactions between microglia and oligodendrocytes bearing α-syn, suggestive of a potential transfer mechanism between microglia and α-syn bearing cells in MSA and the possibility of microglia acting as a mobile vehicle to spread α-syn between anatomically connected brain regions...
April 16, 2018: Molecular and Cellular Neurosciences
Mads N Olesen, Josefine R Christiansen, Steen Vang Petersen, Poul Henning Jensen, Wojciech Paslawski, Marina Romero-Ramos, Vanesa Sanchez-Guajardo
We have previously shown that immunological processes in the brain during α-synuclein-induced neurodegeneration vary depending on the presence or absence of cell death. This suggests that the immune system is able to react differently to the different stages of α-synuclein pathology. However, it was unclear whether these immune changes were governed by brain processes or by a direct immune response to α-synuclein modifications. We have herein locally increased the peripheral concentration of α-synuclein or its pathology-associated variants, nitrated or fibrillar, to characterize the modulation of the CD4 T cell pool by α-synuclein and brain microglia in the absence of any α-synuclein brain pathology...
January 2018: Heliyon
Sing-Hui Ong, Kai-Wey Goh, Cornelius Kwang-Lee Chieng, Yee-How Say
Background: Tumor-induced angiogenesis is an imperative event in pledging new vasculature for tumor metastasis. Since overexpression of neuronal proteins gamma-synuclein (γ-Syn) and cellular prion protein (PrPC ) is always detected in advanced stages of cancer diseases which involve metastasis, this study aimed to investigate whether γ-Syn or PrPC overexpression in colorectal adenocarcinoma, LS 174T cells affects angiogenesis of endothelial cells, EA.hy 926 (EA). Methods: EA cells were treated with conditioned media (CM) of LS 174T-γ-Syn or LS 174T-PrP, and their proliferation, invasion, migration, adhesion and ability to form angiogenic tubes were assessed using a range of biological assays...
2018: PeerJ
Jin-Song He, Ni Xie, Jian-Bo Yang, Hong Guan, Wei-Cai Chen, Chang Zou, Yi-Wen Ouyang, You-Sheng Mao, Xue-Ying Luo, Yue Pan, Li Fu
Breast cancer-specific gene 1 (BCSG1), also referred to as γ-synuclein (SNCG), is highly expressed in human infiltrating breast carcinomas, but not in normal or benign breast tissue. The present study aimed to evaluate the effects of BCSG1 siRNA delivered by lentiviral vector on breast cancer cells and investigate the underlying mechanisms. BCSG1 RNAi lentiviral vector was constructed and transfected into MDA-MB-231 cells. BCSG1 mRNA levels were determined by quantitative polymerase chain reaction analysis...
March 2018: International Journal of Molecular Medicine
Ana I Ramirez, Rosa de Hoz, Elena Salobrar-Garcia, Juan J Salazar, Blanca Rojas, Daniel Ajoy, Inés López-Cuenca, Pilar Rojas, Alberto Triviño, José M Ramírez
Microglia, the immunocompetent cells of the central nervous system (CNS), act as neuropathology sensors and are neuroprotective under physiological conditions. Microglia react to injury and degeneration with immune-phenotypic and morphological changes, proliferation, migration, and inflammatory cytokine production. An uncontrolled microglial response secondary to sustained CNS damage can put neuronal survival at risk due to excessive inflammation. A neuroinflammatory response is considered among the etiological factors of the major aged-related neurodegenerative diseases of the CNS, and microglial cells are key players in these neurodegenerative lesions...
2017: Frontiers in Aging Neuroscience
Ethan Stolzenberg, Deborah Berry, De Yang, Ernest Y Lee, Alexander Kroemer, Stuart Kaufman, Gerard C L Wong, Joost J Oppenheim, Supti Sen, Thomas Fishbein, Ad Bax, Brent Harris, Denise Barbut, Michael A Zasloff
BACKGROUND: Alpha-synuclein (αS) is a nerve cell protein associated with Parkinson disease (PD). Accumulation of αS within the enteric nervous system (ENS) and its traffic from the gut to the brain are implicated in the pathogenesis and progression of PD. αS has no known function in humans and the reason for its accumulation within the ENS is unknown. Several recent studies conducted in rodents have linked αS to immune cell activation in the central nervous system. We hypothesized that αS in the ENS might play a role in the innate immune defenses of the human gastrointestinal (GI) tract...
2017: Journal of Innate Immunity
Natalie R S Goldberg, Samuel E Marsh, Joseph Ochaba, Brandon C Shelley, Hayk Davtyan, Leslie M Thompson, Joan S Steffan, Clive N Svendsen, Mathew Blurton-Jones
Synucleinopathies are a group of neurodegenerative disorders sharing the common feature of misfolding and accumulation of the presynaptic protein α-synuclein (α-syn) into insoluble aggregates. Within this diverse group, Dementia with Lewy Bodies (DLB) is characterized by the aberrant accumulation of α-syn in cortical, hippocampal, and brainstem neurons, resulting in multiple cellular stressors that particularly impair dopamine and glutamate neurotransmission and related motor and cognitive function. Recent studies show that murine neural stem cell (NSC) transplantation can improve cognitive or motor function in transgenic models of Alzheimer's and Huntington's disease, and DLB...
June 2017: Stem Cells Translational Medicine
Hongfei Qiao, Xijing He, Qiaojun Zhang, Ni Zhang, Libo Li, Yanping Hui, Wenjuan Li, Dong Wang, Zhonghen Wu
Microglial cell migration and infiltration plays a critical role in spinal cord injury after thoracoabdominal aortic surgery. In our previous study, α-synuclein, a presynaptic protein was shown to be released from injured neurons and cause microglial cell activation. Here, we aimed to explore the effect of α-synuclein on microglial cell migration. Primary microglial cells were isolated from Sprague-Dawley rats and then exposed different doses (0.2, 0.4, and 0.6 μM) of α-synuclein oligomers. The mRNA and protein levels of HIF-1α were then analyzed by qRT-PCR and Western blot...
January 30, 2017: Journal of Neuroscience Research
Yiqin Ge, Kan Xu
BACKGROUND: The aim of this study is to explore the expression of alpha-synuclein (α-synuclein) in benign, atypical, and anaplastic meningiomas and determine its role in the malignant progression of meningiomas. METHODS: Expression of α-synuclein was measured in 44 meningioma samples by real-time PCR analysis. The effects of overexpression or knockdown of α-synuclein on meningioma cell growth, invasiveness, and tumorigenicity were determined. RESULTS: Atypical and anaplastic meningiomas displayed significantly greater levels of α-synuclein mRNA, relative to benign tumors...
2016: Cancer Cell International
Qiu-Shuang Zhang, Yang Heng, Yu-He Yuan, Nai-Hong Chen
Parkinson's disease (PD) is characterized by α-synuclein accumulation, dopaminergic neuron loss and inflammation. α-Synuclein can be secreted by neurons and activate microglia to different degrees. Excessive microglial activation can increase the production of tumor necrosis factor alpha (TNF-α), interleukin-1-β (IL-1β), interleukin-6 (IL-6), interferon-γ (INF-γ), inducible nitric oxide synthase (iNOS), reactive oxygen species (ROS) and nitric oxide (NO), and can also enhance microglial phagocytosis and migration as well as lymphocyte infiltration...
January 4, 2017: Toxicology Letters
Feng Huang, Shaohua Xu, Qing Ye, Qiuhong Zheng, Yangmei Xu, Qinying Liu
OBJECTIVE: To construct a lentiviral vector carrying the γ-synuclein(SNCG) gene and establish a human colorectal carcinoma cell line SW1116 stably expressing this gene, and then investigate the inhibition of the growth and invasion capacity of SW1116 cells. METHODS: RNA interference fragment was designed according to the SNCG sequence (GenBank: No.NM003087.2), and then SNCG RNAi effective target genes were screened. After the Oligo DNA of target sequences was synthesized, the lentiviral vectors carrying LV-SNCG-RNAi-EGFP (RNAi group) and LV-SNCG-NC-EGFP (NC group) were constructed and packaged to produce lentivirus venom...
April 2016: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
Bryan A Killinger, Anna Moszczynska
The aberrant aggregation of α-synuclein in the brain is a hallmark of Parkinson's disease (PD). In vivo soluble α-synuclein occurs as a monomer and several multimers, the latter of which may be important for the biological function of α-synuclein. Currently, there is a lack of reproducible methods to compare α-synuclein multimer abundance between complex biological samples. Here we developed a method, termed "multimer-PAGE," that combines in-gel chemical cross-linking with several common electrophoretic techniques to measure the stoichiometry of soluble α-synuclein multimers in brain tissue lysates...
April 5, 2016: Analytical Chemistry
J C Cheng, M T Chiang, C H Lee, S Y Liu, K C Chiu, Y T Chou, R Y Huang, S M Huang, Y S Shieh
Dysregulation of γ-synuclein (SNCG) has been reported in many cancers; however, its role in cancer development is still controversial. Here, we examined the potential involvement of DNA methylation in regulating SNCG and its role in oral squamous cell carcinoma (OSCC). We used 8 OSCC cell lines to investigate SNCG methylation and expression. SNCG methylation was examination by methylation-specific polymerase chain reaction and bisulfate sequencing. Cells showing a high degree of SNCG methylation were treated with 5-aza (methylation inhibitor), and changes in their methylation and expression profiles were analyzed...
April 2016: Journal of Dental Research
Sharada Tilve, Francesco Difato, Evelina Chieregatti
Impaired adult neurogenesis and axon traumatic injury participate in the severity of neurodegenerative diseases. Alpha-synuclein, a cytosolic protein involved in Parkinson's disease, may be released from neurons, suggesting a role for excess secreted alpha-synuclein in the onset and spread of the pathology. Here we provide evidence that long term exposure of young neurons to extracellular alpha-synuclein hampers axon elongation and growth cone turning. We show that actin turnover and the rate of movement of actin waves along the axon are altered, due to alpha-synuclein-induced inactivation of cofilin...
November 12, 2015: Scientific Reports
V Siddartha Yerramilli, Suzanne Scarlata
The breast cancer susceptibility gene protein, also known as γ-synuclein, is highly expressed in human breast cancer in a stage-specific manner, with highest expression in late stage cancer. In model systems, γ-synuclein binds phospholipase Cβ2 which is regulated by Gαq to generate intracellular Ca(2+) signals. PLCβ2, which is also absent in normal tissue but highly expressed in breast cancer, is additionally regulated by Rac to promote migration pathways. We have found that γ-synuclein binds to the same region of PLCβ2 as Gαq...
January 2016: Cellular Signalling
Kai He, Peilin Wang
The aim of the present study was to investigate the function of long chain non-coding RNA (lncRNA) in breast cancer cells. Quantitative polymerase chain reaction was used to measure mRNA expression levels in breast cancer tissues, adjacent tissues and in MCF-7 breast cancer cells. Western blot analysis was used to determine the protein expression levels. In addition, a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was employed to measure the rates of cell proliferation. The invasion and migration of the MCF-7 cells were examined using a Transwell® assay...
May 2015: Experimental and Therapeutic Medicine
Yixiao Cai, Christofer Lendel, Lars Österlund, Alex Kasrayan, Lars Lannfelt, Martin Ingelsson, Fredrik Nikolajeff, Mikael Karlsson, Joakim Bergström
The oxidative stress-related reactive aldehydes 4-hydroxy-2-nonenal (HNE) and 4-oxo-2-nonenal (ONE) have been shown to promote formation of α-synuclein oligomers in vitro. However, the changes in secondary structure of α-synuclein and the kinetics of the oligomerization process are not known and were the focus of this study. Size exclusion chromatography showed that after 1 h of incubation, HNE induced the formation of an oligomeric α-synuclein peak with a molecular weight of about ∼2000 kDa, which coincided with a decreasing ∼50 kDa monomeric peak...
August 14, 2015: Biochemical and Biophysical Research Communications
Qing Zhuang, Caiyun Liu, Like Qu, Chengchao Shou
Synuclein-γ (SNCG), a synuclein family member, promotes migration, invasion and metastasis of tumor cells; however, the mechanism remains unclear. The present study investigated the effect of SNCG on malignant phenotypes of MCF7 cells using cell proliferation analysis, cell migration assays and wound healing assays, and verified its effects on extracellular‑signal regulated kinase (Erk) activation and epithelial to mesenchymal transition‑related markers using western blotting. The results indicated that SNCG increased migration (P<0...
September 2015: Molecular Medicine Reports
Shijun Wang, Chun-Hsien Chu, Tessandra Stewart, Carmen Ginghina, Yifei Wang, Hui Nie, Mingri Guo, Belinda Wilson, Jau-Shyong Hong, Jing Zhang
Malformed α-Synuclein (α-syn) aggregates in neurons are released into the extracellular space, activating microglia to induce chronic neuroinflammation that further enhances neuronal damage in α-synucleinopathies, such as Parkinson's disease. The mechanisms by which α-syn aggregates activate and recruit microglia remain unclear, however. Here we show that α-syn aggregates act as chemoattractants to direct microglia toward damaged neurons. In addition, we describe a mechanism underlying this directional migration of microglia...
April 14, 2015: Proceedings of the National Academy of Sciences of the United States of America
Yafang Wang, Xiangqiang Liu, Hongbo Zhang, Li Sun, Yongan Zhou, Haifeng Jin, Hongwei Zhang, Hui Zhang, Jiaming Liu, Hao Guo, Yongzhan Nie, Kaichun Wu, Daiming Fan, Helong Zhang, Lili Liu
Hypoxia has been implicated as a crucial microenvironmental factor that induces cancer metastasis. We previously reported that hypoxia could promote gastric cancer (GC) metastasis, but the underlying mechanisms are not clear. Long noncoding RNAs (lncRNAs) have recently emerged as important regulators of carcinogenesis that act on multiple pathways. However, whether lncRNAs are involved in hypoxia-induced GC metastasis remains unknown. In this study, we investigated the differentially expressed lncRNAs resulting from hypoxia-induced GC and normoxia conditions using microarrays and validated our results through real-time quantitative polymerase chain reaction...
December 2014: Neoplasia: An International Journal for Oncology Research
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