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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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...
October 1, 2016: Ageing Research Reviews
https://www.readbyqxmd.com/read/27646849/identification-of-antisense-long-noncoding-rnas-that-function-as-sineups-in-human-cells
#7
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...
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
#8
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...
September 12, 2016: Animal Genetics
https://www.readbyqxmd.com/read/27613482/silica-nanoparticles-induce-alpha-synuclein-induction-and-aggregation-in-pc12-cells
#9
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
#10
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
#11
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
#12
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
#13
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
https://www.readbyqxmd.com/read/27294386/genetic-mutation-analysis-of-parkinson-s-disease-patients-using-multigene-next-generation-sequencing-panels
#14
Ana Gorostidi, José Félix Martí-Massó, Alberto Bergareche, Mari Cruz Rodríguez-Oroz, Adolfo López de Munain, Javier Ruiz-Martínez
BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disorder, affecting millions of people. Genome-wide association studies (GWAS) have found >25 genetic risk factors and at least 15 loci directly associated with PD. Recent advances in new next-generation DNA sequencing technologies, such as the semiconductor-based Ion Torrent platform, make multigene sequencing cheaper, faster, and more reliable. OBJECTIVES: Our objective was to test the power of this next-generation sequencing technology to analyze large samples by screening the majority of the most relevant PD-related genes known for single and compound mutations...
October 2016: Molecular Diagnosis & Therapy
https://www.readbyqxmd.com/read/27260470/amelioration-of-neuronal-cell-death-in-a-spontaneous-obese-rat-model-by-dietary-restriction-through-modulation-of-ubiquitin-proteasome-system
#15
Karnam Shruthi, S Sreenivasa Reddy, P Yadagiri Reddy, Potula Shivalingam, Nemani Harishankar, G Bhanuprakash Reddy
Dietary restriction (DR) has been shown to increase longevity, delay onset of aging, reduce DNA damage and oxidative stress and prevent age-related decline of neuronal activity. We previously reported the role of altered ubiquitin proteasome system (UPS) in the neuronal cell death in a spontaneous obese rat model (WNIN/Ob rat). In this study, we investigated the effect of DR on obesity-induced neuronal cell death in a rat model. Two groups of 40-day-old WNIN/Ob rats were either fed ad libitum (Ob) or pair-fed with lean...
July 2016: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/27231703/absence-of-uchl-1-function-leads-to-selective-motor-neuropathy
#16
Barış Genç, Javier H Jara, Megan C Schultz, Marin Manuel, Macdonell J Stanford, Mukesh Gautam, Jodi L Klessner, Gabriella Sekerkova, Daniel B Heller, Gregory A Cox, Charles J Heckman, Christine J DiDonato, P Hande Özdinler
OBJECTIVE: The aim of this study was to investigate the role of ubiquitin C-terminal hydrolase-L1 (UCHL1) for motor neuron circuitry and especially in spinal motor neuron (SMN) health, function, and connectivity. METHODS: Since mutations in UCHL1 gene leads to motor dysfunction in patients, we investigated the role of UCHL1 on SMN survival, axon health, and connectivity with the muscle, by employing molecular and cellular marker expression analysis and electrophysiological recordings, in healthy wild-type and Uchl1 (nm3419) (UCHL1-/-) mice, which lack all UCHL1 function...
May 2016: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/27206673/reprogramming-human-a375-amelanotic-melanoma-cells-by-catalase-overexpression-upregulation-of-antioxidant-genes-correlates-with-regression-of-melanoma-malignancy-and-with-malignant-progression-when-downregulated
#17
Candelaria Bracalente, Irene L Ibañez, Ariel Berenstein, Cintia Notcovich, María B Cerda, Fabio Klamt, Ariel Chernomoretz, Hebe Durán
Reactive oxygen species (ROS) are implicated in tumor transformation. The antioxidant system (AOS) protects cells from ROS damage. However, it is also hijacked by cancers cells to proliferate within the tumor. Thus, identifying proteins altered by redox imbalance in cancer cells is an attractive prognostic and therapeutic tool. Gene expression microarrays in A375 melanoma cells with different ROS levels after overexpressing catalase were performed. Dissimilar phenotypes by differential compensation to hydrogen peroxide scavenging were generated...
July 5, 2016: Oncotarget
https://www.readbyqxmd.com/read/27180120/effect-of-age-on-expression-of-spermatogonial-markers-in-bovine-testis-and-isolated-cells
#18
Mariana Ianello Giassetti, Marcelo Demarchi Goissis, Pedro Vale Moreira, Flavia Regina Oliveira de Barros, Mayra Elena Ortiz D'Ávila Assumpção, José Antônio Visintin
Spermatogonial stem cells (SSC) are the most undifferentiated germ cell present in adult male testes and, it is responsible to maintain the spermatogenesis. Age has a negative effect over stem cell, but the aging effect on SSC is not elucidated for bovine. The present study aim to evaluate the effect of age on the expression of undifferentiated spermatogonial markers in testis and in enriched testicular cells from prepubertal calves and adult bulls. In this matter, testicular parenchyma from calves (3-5 months) (n=5) and bulls with 3 years of age (n=5) were minced and, isolated cells were obtained after two enzymatic digestions...
July 2016: Animal Reproduction Science
https://www.readbyqxmd.com/read/27129396/conservation-of-spermatogonial-stem-cell-marker-expression-in-undifferentiated-felid-spermatogonia
#19
Lindsey M Vansandt, Janelle L Livesay, Melissa Joy Dickson, Lei Li, Budhan S Pukazhenthi, Carol L Keefer
Spermatogonial stem cells (SSCs) are distinct in their ability to self-renew, transmit genetic information, and persist throughout the life of an individual. These characteristics make SSCs a useful tool for addressing diverse challenges such as efficient transgenic production in nonrodent, biomedical animal models, or preservation of the male genome for species in which survival of frozen-thawed sperm is low. A requisite first step to access this technology in felids is the establishment of molecular markers...
September 1, 2016: Theriogenology
https://www.readbyqxmd.com/read/26965686/other-proteins-involved-in-parkinson-s-disease-and-related-disorders
#20
Fernando Cardona, Jordi Pérez-Tur
In order to explain the molecular causes of Parkinson's Disease (PD) it is important to understand the effect that mutations described as causative of the disease have at the functional level. In this special issue, several authors have been reviewing the effects in PD and other parkinsonisms of mutations described in LRRK2, α-synuclein, PINK1-Parkin-DJ-1, UCHL1, ATP13A2, GBA, VPS35, FBOX7 and HTRA2. In this review, we compile the knowledge about other proteins with a more general role in neurodegenerative diseases (MAPT) or for which less data is available due to its recent discovery (EIF4G1, DNAJC13), the lack of structural or functional data (as for PLA2G6 or DNAJC6), or even their doubtful association with the disease (as for GIGYF2, SYNJ1 and SPR)...
March 11, 2016: Current Protein & Peptide Science
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