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https://www.readbyqxmd.com/read/28334853/novel-uchl1-mutations-reveal-new-insights-into-ubiquitin-processing
#1
Siri L Rydning, Paul H Backe, Mirta M L Sousa, Zafar Iqbal, Ane-Marte Øye, Ying Sheng, Mingyi Yang, Xiaolin Lin, Geir Slupphaug, Tonje H Nordenmark, Magnus D Vigeland, Magnar Bjørås, Chantal M Tallaksen, Kaja K Selmer
No abstract text is available yet for this article.
March 9, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28300150/s-nitrosylation-of-uchl1-induces-its-structural-instability-and-promotes-%C3%AE-synuclein-aggregation
#2
Roshan Kumar, Deepak K Jangir, Garima Verma, Shashi Shekhar, Pranita Hanpude, Sanjay Kumar, Raniki Kumari, Nirpendra Singh, Neel Sarovar Bhavesh, Nihar Ranjan Jana, Tushar Kanti Maiti
Ubiquitin C-terminal Hydrolase-1 (UCHL1) is a deubiquitinating enzyme, which plays a key role in Parkinson's disease (PD). It is one of the most important proteins, which constitute Lewy body in PD patient. However, how this well folded highly soluble protein presents in this proteinaceous aggregate is still unclear. We report here that UCHL1 undergoes S-nitrosylation in vitro and rotenone induced PD mouse model. The preferential nitrosylation in the Cys 90, Cys 152 and Cys 220 has been observed which alters the catalytic activity and structural stability...
March 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28296235/the-circular-rna-cirs-7-promotes-app-and-bace1-degradation-in-an-nf-%C3%AE%C2%BAb-dependent-manner
#3
Zhemin Shi, Ting Chen, Qingbin Yao, Lina Zheng, Zhen Zhang, Jingzhao Wang, Zhimei Hu, Hongmei Cui, Yawei Han, Xiaohui Han, Kun Zhang, Wei Hong
The aberrant accumulation of β-amyloid peptide (Aβ) in the brain is a key feature of Alzheimer's disease (AD), and enhanced cleavage of β-amyloid precursor protein (APP) by β-site APP-cleaving enzyme 1 (BACE1) has a major causative role in AD. Despite their prominence in AD pathogenesis, the regulation of BACE1 and APP is incompletely understood. In this study, we report that the circular RNA circular RNA sponge for miR-7 (ciRS-7) has an important role in regulating BACE1 and APP protein levels. Previous studies have shown that ciRS-7, which is highly expressed in the human brain, is down-regulated in the brain of people with AD but the relevance of this finding was not clear...
March 13, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28226265/alterations-of-ubiquitin-related-proteins-in-the-pathology-and-development-of-schizophrenia-evidence-from-human-and-animal-studies
#4
Jessica L Andrews, Frederic J Goodfellow, Natalie Matosin, Mollie K Snelling, Kelly A Newell, Xu-Feng Huang, Francesca Fernandez-Enright
Gene expression analyses in post-mortem schizophrenia brains suggest that a number of ubiquitin proteasome system (UPS) genes are associated with schizophrenia; however the status of UPS proteins in the schizophrenia brain is largely unknown. Ubiquitin related proteins are inherently involved in memory, neuronal survival and morphology, which are processes implicated in neurodevelopmental disorders such as schizophrenia. We examined levels of five UPS proteins (Protein Inhibitor of Activated STAT2 [PIAS2], F-Box and Leucine rich repeat protein 21 [FBXL21], Mouse Double Minute 2 homolog [MDM2], Ubiquitin Carboxyl-Terminal Hydrolase-L1 [UCHL1] and Ubiquitin Conjugating Enzyme E2D1 [UBE2D1]) involved in these neuronal processes, within the dorsolateral prefrontal cortex of post-mortem schizophrenia subjects and matched controls (n = 30/group), in addition to across neurodevelopmental time-points (juvenile, adolescent and adult stages of life), utilizing a well-established neurodevelopmental phencyclidine (PCP) animal model of schizophrenia...
January 18, 2017: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/28193576/overexpression-of-ubiquitin-carboxyl-terminal-hydrolase-l1-uchl1-in-serum-of-children-after-thermal-injury
#5
Ewa Matuszczak, Marzena Tylicka, Wojciech Dębek, Anna Sankiewicz, Ewa Gorodkiewicz, Adam Hermanowicz
PURPOSE: The study aims to determinate concentrations of ubiquitin C-terminal hydrolase 1 (UCHL1), which hydrolyzes amino acids from ubiquitin and cleave di-ubiquitins, in serum of children after thermal injury. PATIENTS/METHODS: 42 children scalded by hot water, managed at the Department of Pediatric Surgery, with burns in 4-20% TBSA were included into the study (age 9 months up to 14 years, mean age 2.5±1 years). Blood plasma UCHL1 concentration was assessed in 2-6h, 12-16h, 3d, 5d, and 7d after injury using surface plasmon resonance imaging biosensor...
February 10, 2017: Advances in Medical Sciences
https://www.readbyqxmd.com/read/28129614/effects-of-titanium-dioxide-nanoparticles-exposure-on-parkinsonism-in-zebrafish-larvae-and-pc12
#6
Qinglian Hu, Fengliang Guo, Fenghui Zhao, Zhengwei Fu
Nanomaterials hold significant potential for industrial and biomedical application these years. Therefore, the relationship between nanoparticles and neurodegenerative disease is of enormous interest. In this contribution, zebrafish embryos and PC12 cell lines were selected for studying neurotoxicity of titanium dioxide nanoparticles (TiO2 NPs). After exposure of different concentrations of TiO2 NPs to embryos from fertilization to 96 hpf, the hatching time of zebrafish was decreased, accompanied by an increase in malformation rate...
January 16, 2017: Chemosphere
https://www.readbyqxmd.com/read/28117141/influence-of-exposure-to-coarse-fine-and-ultrafine-urban-particulate-matter-and-their-biological-constituents-on-neural-biomarkers-in-a-randomized-controlled-crossover-study
#7
Ling Liu, Bruce Urch, Mieczyslaw Szyszkowicz, Mary Speck, Karen Leingartner, Robin Shutt, Guillaume Pelletier, Diane R Gold, James A Scott, Jeffrey R Brook, Peter S Thorne, Frances S Silverman
BACKGROUND: Epidemiological studies have reported associations between air pollution and neuro-psychological conditions. Biological mechanisms behind these findings are still not clear. OBJECTIVES: We examined changes in blood and urinary neural biomarkers following exposure to concentrated ambient coarse, fine and ultrafine particles. METHODS: Fifty healthy non-smoking volunteers, mean age 28years, were exposed to coarse (2.5-10μm, mean 213μg/m(3)) and fine (0...
April 2017: Environment International
https://www.readbyqxmd.com/read/28074940/alpha7-nicotinic-acetylcholine-receptor-is-required-for-amyloid-pathology-in-brain-endothelial-cells-induced-by-glycoprotein-120-methamphetamine-and-nicotine
#8
Liqun Liu, Jingyi Yu, Li Li, Bao Zhang, Lingjuan Liu, Chun-Hua Wu, Ambrose Jong, Ding-An Mao, Sheng-He Huang
One of the most challenging issues in HIV-associated neurocognitive disorders (HAND) caused by HIV-1 virotoxins and drug abuse is the lack of understanding the underlying mechanisms that are commonly associated with disorders of the blood-brain barrier (BBB), which mainly consists of brain microvascular endothelial cells (BMEC). Here, we hypothesized that Glycoprotein 120 (gp120), methamphetamine (METH) and nicotine (NT) can enhance amyloid-beta (Aβ) accumulation in BMEC through Alpha7 nicotinic acetylcholine receptor (α7 nAChR)...
January 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28007905/novel-uchl1-mutations-reveal-new-insights-into-ubiquitin-processing
#9
Siri L Rydning, Paul H Backe, Mirta M L Sousa, Zafar Iqbal, Ane-Marte Øye, Ying Sheng, Mingyi Yang, Xiaolin Lin, Geir Slupphaug, Tonje H Nordenmark, Magnus D Vigeland, Magnar Bjørås, Chantal M Tallaksen, Kaja K Selmer
Recessive loss of function of the neuronal ubiquitin hydrolase UCHL1 has been implicated in early-onset progressive neurodegeneration (MIM no. 615491), so far only in one family. In this study a second family is characterized, and the functional consequences of the identified mutations in UCHL1 are explored. Three siblings developed childhood-onset optic atrophy, followed by spasticity and ataxia. Whole exome sequencing identified compound heterozygous variants in UCHL1, c.533G>A (p.Arg178Gln) and c.647C>A (p...
December 22, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27999335/mutant-cag-repeats-effectively-targeted-by-rna-interference-in-sca7-cells
#10
Agnieszka Fiszer, Joanna P Wroblewska, Bartosz M Nowak, Wlodzimierz J Krzyzosiak
Spinocerebellar ataxia type 7 (SCA7) is a human neurodegenerative polyglutamine (polyQ) disease caused by a CAG repeat expansion in the open reading frame of the ATXN7 gene. The allele-selective silencing of mutant transcripts using a repeat-targeting strategy has previously been used for several polyQ diseases. Herein, we demonstrate that the selective targeting of a repeat tract in a mutant ATXN7 transcript by RNA interference is a feasible approach and results in an efficient decrease of mutant ataxin-7 protein in patient-derived cells...
December 17, 2016: Genes
https://www.readbyqxmd.com/read/27935410/establishment-of-a-high-throughput-detection-system-for-dna-demethylating-agents
#11
Eriko Okochi-Takada, Naoko Hattori, Akihiro Ito, Tohru Niwa, Mika Wakabayashi, Kana Kimura, Minoru Yoshida, Toshikazu Ushijima
Epigenetic alterations underlie various human disorders, including cancer, and this has resulted in the development of drugs targeting epigenetic alterations. Although DNA demethylating agents are one of the major epigenetic drugs, only two compounds-5-azacytidine (5-aza-CR, azacitidine) and 5-aza-2'-deoxycytidine (5-aza-dC, decitabine)-have obtained clinical approval. Here, we aimed to establish a detection system for DNA demethylating agents suitable for a high-throughput screening (HTS) in mammalian cells...
December 9, 2016: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/27857231/quantitative-proteomic-analysis-of-age-related-subventricular-zone-proteins-associated-with-neurodegenerative-disease
#12
Xianli Wang, Chuanming Dong, Lixin Sun, Liang Zhu, Chenxi Sun, Rongjie Ma, Ke Ning, Bing Lu, Jinfu Zhang, Jun Xu
Aging is characterized by a progressive decline in the function of adult tissues which can lead to neurodegenerative disorders. However, little is known about the correlation between protein changes in the subventricular zone (SVZ) and neurodegenerative diseases with age. In the present study, neural stem cells (NSCs) were derived from the SVZ on postnatal 7 d, 1 m, and 12 m-old mice. With age, NSCs exhibited increased SA-β-gal activity and decreased proliferation and pool size in the SVZ zone, and were associated with elevated inflammatory chemokines and cytokines...
November 18, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27702698/life-and-death-in-the-trash-heap-the-ubiquitin-proteasome-pathway-and-uchl1-in-brain-aging-neurodegenerative-disease-and-cerebral-ischemia
#13
REVIEW
Steven H Graham, Hao Liu
The ubiquitin proteasome pathway (UPP) is essential for removing abnormal proteins and preventing accumulation of potentially toxic proteins within the neuron. UPP dysfunction occurs with normal aging and is associated with abnormal accumulation of protein aggregates within neurons in neurodegenerative diseases. Ischemia disrupts UPP function and thus may contribute to UPP dysfunction seen in the aging brain and in neurodegenerative diseases. Ubiquitin carboxy-terminal hydrolase L1 (UCHL1), an important component of the UPP in the neuron, is covalently modified and its activity inhibited by reactive lipids produced after ischemia...
March 2017: Ageing Research Reviews
https://www.readbyqxmd.com/read/27646849/identification-of-antisense-long-noncoding-rnas-that-function-as-sineups-in-human-cells
#14
Aleks Schein, Silvia Zucchelli, Sakari Kauppinen, Stefano Gustincich, Piero Carninci
Mammalian genomes encode numerous natural antisense long noncoding RNAs (lncRNAs) that regulate gene expression. Recently, an antisense lncRNA to mouse Ubiquitin carboxyl-terminal hydrolase L1 (Uchl1) was reported to increase UCHL1 protein synthesis, representing a new functional class of lncRNAs, designated as SINEUPs, for SINE element-containing translation UP-regulators. Here, we show that an antisense lncRNA to the human protein phosphatase 1 regulatory subunit 12A (PPP1R12A), named as R12A-AS1, which overlaps with the 5' UTR and first coding exon of the PPP1R12A mRNA, functions as a SINEUP, increasing PPP1R12A protein translation in human cells...
September 20, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27615062/identification-of-new-single-nucleotide-polymorphisms-affecting-total-number-born-and-candidate-genes-related-to-ovulation-rate-in-chinese-erhualian-pigs
#15
L C He, P H Li, X Ma, S P Sui, S Gao, S W Kim, Y Q Gu, Y Huang, N S Ding, R H Huang
The Chinese Erhualian pig has the highest record for litter size in the world. However, the genetic mechanism of its high prolificacy remains poorly understood. In our study, large phenotypic variations in litter size were found among Erhualian sows. Significant differences in total number born (TNB) and corpora lutea numbers were observed between sows with high and low estimated breeding values (EBVs) for TNB. To identify single nucleotide polymorphisms (SNPs) associated with TNB, a selective genomic scan was conducted on 18 sows representing the top 10% and 18 sows representing the bottom 10% of EBVs of 177 sows using Illumina Porcine SNP60 genotype data...
February 2017: Animal Genetics
https://www.readbyqxmd.com/read/27613482/silica-nanoparticles-induce-alpha-synuclein-induction-and-aggregation-in-pc12-cells
#16
Hongjun Xie, Jie Wu
Silica nanoparticles (SiO2-NPs) are widely applied in diagnosis, imaging, and drug delivery of central nervous diseases. Previously, we found that SiO2-NPs enter the brain and, more specifically, the dopaminergic neurons in the striatum. Whether SiO2-NPs have neurotoxicity and contribute to development of Parkinson's disease (PD) remains unclear. In this study, we investigated the effect of SiO2-NPs on PC12 cells, a dopaminergic neuron-like cell line. We showed that SiO2-NPs up-regulated α-synuclein expression, and N-acetyl cysteine reduced α-synuclein...
October 25, 2016: Chemico-biological Interactions
https://www.readbyqxmd.com/read/27525927/isolation-proliferation-and-induction-of-bama-mini-pig-spermatogonial-stem-cells-in-vitro
#17
H M Zhao, H Yang, F H Luo, M X Li, S Zhang, X G Yang, Y Q Lu, S S Lu, Y J Wu, K H Lu
Spermatogonial stem cells (SSCs), the unique seed cells of testes, can undergo meiosis and form spermatozoa, thus transmitting genetic information to offspring. Research concerning these cells explores the mechanism underlying spermatogenesis, making possible the induction of their differentiation into spermatozoa in vitro. SSCs have therefore attracted much interest among scientists. Although the proliferation of such cells in vitro has been demonstrated, we are unaware of any long-term laboratory culture of porcine SSCs...
August 12, 2016: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/27508024/inhibition-of-spinal-uchl1-attenuates-pain-facilitation-in-a-cancer-induced-bone-pain-model-by-inhibiting-ubiquitin-and-glial-activation
#18
Wei Cheng, Yuan-Li Chen, Liang Wu, Bei Miao, Qin Yin, Jin-Feng Wang, Zhi-Jian Fu
The present study examined alterations of spinal ubiquitin C-terminal hydrolase L1 (UCHL1), ubiquitin expression and glial activation in the cancer-induced bone pain rats. Furthermore, whether inhibition of spinal UCHL1 could alleviate cancer-induced bone pain was observed. The CIBP model was established by intrathecal Walker 256 mammary gland carcinoma cells in SD rats. The rats of CIBP developed significant pain facilitation in the Von Frey test. Double immunofluorescence analyses revealed that in the spines of CIBP rats, ubiquitin co-localized with NeuN, Iba-1 or GFAP; UCHL1 and NeuN were co-expressed and UCHL1 also co-localized with ubiquitin...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27338628/the-long-non-coding-rnas-in-neurodegenerative-diseases-novel-mechanisms-of-pathogenesis
#19
Paola Riva, Antonia Ratti, Marco Venturin
BACKGROUND: Long-non-coding RNAs (lncRNAs), RNA molecules longer than 200 nucleotides, have been involved in several biological processes and in a growing number of diseases, controlling gene transcription, pre-mRNA processing, the transport of mature mRNAs to specific cellular compartments, the regulation of mRNA stability, protein translation and turnover. The fundamental role of lncRNAs in central nervous system (CNS) is becoming increasingly evident. LncRNAs are abundantly expressed in mammalian CNS in a specific spatio-temporal manner allowing a quick response to environmental/molecular changes...
2016: Current Alzheimer Research
https://www.readbyqxmd.com/read/27324898/protein-profile-and-morphological-alterations-in-penumbra-after-focal-photothrombotic-infarction-in-the-rat-cerebral-cortex
#20
Anatoly Uzdensky, Svetlana Demyanenko, Grigory Fedorenko, Tayana Lapteva, Alexej Fedorenko
After ischemic stroke, cell damage propagates from infarct core to surrounding tissues (penumbra). To reveal proteins involved in neurodegeneration and neuroprotection in penumbra, we studied protein expression changes in 2-mm ring around the core of photothrombotic infarct induced in the rat brain cortex by local laser irradiation after administration of Bengal Rose. The ultrastructural study showed edema and degeneration of neurons, glia, and capillaries. Morphological changes gradually decreased across the penumbra...
June 21, 2016: Molecular Neurobiology
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