keyword
MENU ▼
Read by QxMD icon Read
search

HTT

keyword
https://www.readbyqxmd.com/read/28930690/the-self-inactivating-kamicas9-system-for-the-editing-of-cns-disease-genes
#1
Nicolas Merienne, Gabriel Vachey, Lucie de Longprez, Cécile Meunier, Virginie Zimmer, Guillaume Perriard, Mathieu Canales, Amandine Mathias, Lucas Herrgott, Tim Beltraminelli, Axelle Maulet, Thomas Dequesne, Catherine Pythoud, Maria Rey, Luc Pellerin, Emmanuel Brouillet, Anselme L Perrier, Renaud du Pasquier, Nicole Déglon
Neurodegenerative disorders are a major public health problem because of the high frequency of these diseases. Genome editing with the CRISPR/Cas9 system is making it possible to modify the sequence of genes linked to these disorders. We designed the KamiCas9 self-inactivating editing system to achieve transient expression of the Cas9 protein and high editing efficiency. In the first application, the gene responsible for Huntington's disease (HD) was targeted in adult mouse neuronal and glial cells. Mutant huntingtin (HTT) was efficiently inactivated in mouse models of HD, leading to an improvement in key markers of the disease...
September 19, 2017: Cell Reports
https://www.readbyqxmd.com/read/28928661/ginkgo-biloba-extract-gbe-stimulates-the-hypothalamic-serotonergic-system-and-attenuates-obesity-in-ovariectomized-rats
#2
Renata M Banin, Iracema S de Andrade, Suzete M Cerutti, Lila M Oyama, Mônica M Telles, Eliane B Ribeiro
Menopause is associated with increased risk to develop obesity but the mechanisms involved are not fully understood. We have shown that Ginkgo biloba extract (GbE) improved diet-induced obesity. Since GbE might be effective in the treatment of obesity related to menopause, avoiding the side effects of hormone replacement therapy, we investigated the effect of GbE on hypothalamic systems controlling energy homeostasis. Wistar rats were either ovariectomized (OVX) or Sham-operated. After 2 months, either 500 mg...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28920889/therapies-targeting-dna-and-rna-in-huntington-s-disease
#3
REVIEW
Edward J Wild, Sarah J Tabrizi
No disease-slowing treatment exists for Huntington's disease, but its monogenic inheritance makes it an appealing candidate for the development of therapies targeting processes close to its genetic cause. Huntington's disease is caused by CAG repeat expansions in the HTT gene, which encodes the huntingtin protein; development of therapies to target HTT transcription and the translation of its mRNA is therefore an area of intense investigation. Huntingtin-lowering strategies include antisense oligonucleotides and RNA interference targeting mRNA, and zinc finger transcriptional repressors and CRISPR-Cas9 methods aiming to reduce transcription by targeting DNA...
October 2017: Lancet Neurology
https://www.readbyqxmd.com/read/28920551/a-comprehensive-in-silico-analysis-of-huntingtin-and-its-interactome
#4
Valentina Brandi, Valentina Di Lella, Maria Marino, Paolo Ascenzi, Fabio Polticelli
A polyglutamine expansion of the N-terminal region of huntingtin (Htt) causes Huntington's disease (HD), a severe neurodegenerative disorder. Htt huge multidomain structure, the presence of disordered regions, and the lack of sequence homologs of known structure, so far prevented structural studies of Htt, making the study of its structure-function relationships very difficult. In this work, the presence and location of five Htt ordered domains (named from Hunt1 to Hunt5) has been detected and the structure of these domains has been predicted for the first time using a combined threading/ab initio modelling approach...
September 18, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28900136/differential-effects-of-soluble-and-aggregating-polyq-proteins-on-cytotoxicity-and-type-1-myosin-dependent-endocytosis-in-yeast
#5
Lisa L Berglund, Xinxin Hao, Beidong Liu, Julie Grantham, Thomas Nyström
Huntington's disease develops when the polyglutamine (polyQ) repeat in the Huntingtin (Htt) protein is expanded to over 35 glutamines rendering it aggregation-prone. Here, using Htt exon-1 as a polyQ model protein in a genome-wide screen in yeast, we show that the normal and soluble Htt exon-1 is toxic in cells with defects in type-1 myosin-dependent endocytosis. The toxicity of Htt is linked to physical interactions with type-1 myosins, which occur via the Htt proline-rich region, leading to a reduction in actin patch polarization and clathrin-dependent endocytosis...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28900094/-protein-protein-interactions-of-huntingtin-in-the-hippocampus
#6
A L Proskura, S O Vechkapova, T A Zapara, A S Ratushniak
Huntingtin (HTT) occurs in the neuronal cytoplasm and can interact with structural elements of synapses. Huntington's disease (HD) results from pathological expansion of a polyglutamine stretch in the HTT molecule, being probably associated with aberrant protein-protein interactions. The pathogenetic mechanism is still incompletely understood. Alterations of the synaptic structure and plasticity in the hippocampus are observed in early HD. The objective of the study was to theoretically evaluate the HTT contribution to changes in synaptic plasticity by integrating the available experimental data...
July 2017: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/28890225/early-life-stress-predicts-negative-urgency-through-brooding-depending-on-5-httlpr-genotype-a-pilot-study-with-6-month-follow-up-examining-suicide-ideation
#7
Jorge Valderrama, Regina Miranda
The present study examined the interaction between early life stress and 5-HTT genotypes in predicting two risk factors for suicidal behavior - the brooding subtype of rumination and impulsivity, in the form of negative urgency - over time. Furthermore, we examined early life stress, brooding, and impulsivity as predictors of suicidal ideation over time. Participants with and without a history of early life stress were genotyped for the 5-HTTLPR polymorphism and completed assessments assessing brooding and negative urgency at baseline and 6-month follow up...
September 1, 2017: Psychiatry Research
https://www.readbyqxmd.com/read/28889265/manganese-and-the-insulin-igf-signaling-network-in-huntington-s-disease-and-other-neurodegenerative-disorders
#8
Miles R Bryan, Aaron B Bowman
Huntington's disease (HD) is an autosomal dominant neurodegenerative disease resulting in motor impairment and death in patients. Recently, several studies have demonstrated insulin or insulin-like growth factor (IGF) treatment in models of HD, resulting in potent amelioration of HD phenotypes via modulation of the PI3K/AKT/mTOR pathways. Administration of IGF and insulin can rescue microtubule transport, metabolic function, and autophagy defects, resulting in clearance of Huntingtin (HTT) aggregates, restoration of mitochondrial function, amelioration of motor abnormalities, and enhanced survival...
2017: Advances in Neurobiology
https://www.readbyqxmd.com/read/28867940/genetics-of-generalized-anxiety-disorder-and-related-traits
#9
Michael G Gottschalk, Katharina Domschke
This review serves as a systematic guide to the genetics of generalized anxiety disorder (GAD) and further focuses on anxiety-relevant endophenotypes, such as pathological worry fear of uncertainty, and neuroticism. We inspect clinical genetic evidence for the familialityl heritability of GAD and cross-disorder phenotypes based on family and twin studies. Recent advances of linkage studies, genome-wide association studies, and candidate gene studies (eg, 5-HTT, 5-HT1A, MAOA, BDNF) are outlined. Functional and structural neuroimaging and neurophysiological readouts relating to peripheral stress markers and psychophysiology are further integrated, building a multilevel disease framework...
June 2017: Dialogues in Clinical Neuroscience
https://www.readbyqxmd.com/read/28858902/huntington-mice-demonstrate-diminished-pain-response-in-inflammatory-pain-model
#10
Ya-Chi Lin, Hung-Tsung Hsiao, Sheng-Nan Wu, Yen-Chin Liu
BACKGROUND: Huntington disease (HD) affects the nervous system and leads to mental and motor dysfunction. Previous studies have shown that HD is caused by the exon 1 region of the huntingtin (HTT) gene having expanded CAG trinucleotide repeats. However, few studies have focused on the relationship between HD and pain. The purpose of this study is to investigate the relationship between HD and pain response. METHODS: We used clinical similar transgenic HD mice carrying a mutant HTT exon 1 containing 84 CAG trinucleotide repeats to evaluate the relationship between HD and pain...
August 30, 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28855976/antioxidant-effects-of-a-hydroxytyrosol-based-pharmaceutical-formulation-on-body-composition-metabolic-state-and-gene-expression-a-randomized-double-blinded-placebo-controlled-crossover-trial
#11
Carmela Colica, Laura Di Renzo, Domenico Trombetta, Antonella Smeriglio, Sergio Bernardini, Giorgia Cioccoloni, Renata Costa de Miranda, Paola Gualtieri, Paola Sinibaldi Salimei, Antonino De Lorenzo
Hydroxytyrosol (HT) plays a significant role in cardiovascular disease (CVD) protection, and its metabolites are able to protect from the endothelial dysfunction commonly present in atherosclerosis. This randomized double-blinded, placebo-controlled crossover trial determined the effect in healthy volunteers of two gastroresistant capsules containing 15 mg/day of HT, for a 3-week period (HTT). Evaluation of nutritional status, serum metabolites, oxidative stress biomarkers, and gene expression of 9 genes related to oxidative stress, inflammation, and CVDs was performed...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28841744/-hope-for-huntington-s-disease-patients-first-clinical-gene-silencing-study-in-progress
#12
Jens D Rollnik
Huntington's disease (HD) is an autosomal-dominant inherited neurodegenerative disorder, characterized by motor, psychiatric and cognitive symptoms for which as yet no causal treatment is available. It has a prevalence of 1 : 10 000 in Germany. Its cause is a mutation in the Huntington gene (CAG-repeat). The mutation induces a polyglutamine expansion in the huntingtin protein (HTT). Mutant HTT (mHTT) has cytotoxic properties, aggregates in the cell and leads to complex pathophysiological disturbances ending in cell death...
August 2017: Fortschritte der Neurologie-Psychiatrie
https://www.readbyqxmd.com/read/28840144/transtibial-versus-anteromedial-portal-acl-reconstruction-is-a-hybrid-approach-the-best
#13
Jonathan K Jennings, Daniel P Leas, James E Fleischli, Donald F D'Alessandro, Richard D Peindl, Dana P Piasecki
BACKGROUND: Improved biomechanical and clinical outcomes are seen when the femoral tunnels of the anterior cruciate ligament (ACL) are placed in the center of the femoral insertion. The transtibial (TT) technique has been shown to be less capable of this than an anteromedial (AM) portal approach but is more familiar to surgeons and less technically challenging. A hybrid transtibial (HTT) technique using medial portal guidance of a transtibial guide wire without knee hyperflexion may offer anatomic tunnel placement while maintaining the relative ease of a TT technique...
August 2017: Orthopaedic Journal of Sports Medicine
https://www.readbyqxmd.com/read/28832564/haplotype-based-stratification-of-huntington-s-disease
#14
Michael J Chao, Tammy Gillis, Ranjit S Atwal, Jayalakshmi Srinidhi Mysore, Jamshid Arjomand, Denise Harold, Peter Holmans, Lesley Jones, Michael Orth, Richard H Myers, Seung Kwak, Vanessa C Wheeler, Marcy E MacDonald, James F Gusella, Jong-Min Lee
Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by expansion of a CAG trinucleotide repeat in HTT, resulting in an extended polyglutamine tract in huntingtin. We and others have previously determined that the HD-causing expansion occurs on multiple different haplotype backbones, reflecting more than one ancestral origin of the same type of mutation. In view of the therapeutic potential of mutant allele-specific gene silencing, we have compared and integrated two major systems of HTT haplotype definition, combining data from 74 sequence variants to identify the most frequent disease-associated and control chromosome backbones and revealing that there is potential for additional resolution of HD haplotypes...
August 23, 2017: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/28821645/mutant-huntingtin-is-secreted-via-a-late-endosomal-lysosomal-unconventional-secretory-pathway
#15
Katarina Trajkovic, Hyunkyong Jeong, Dimitri Krainc
Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by the expansion of a CAG triplet in the gene encoding for huntingtin. The resulting mutant protein huntingtin (mHtt) with extended polyglutamine (polyQ) sequence at the N-terminus leads to neuronal degeneration both in cell-autonomous and non-cell-autonomous manners. Recent studies identified mHtt in the extracellular environment and suggested that its spreading contributes to toxicity, but the mechanism of mHtt release from the cell of origin remains unknown...
August 16, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28811068/a-positron-emission-tomography-study-of-the-serotonergic-system-in-relation-to-anxiety-in-depression
#16
Zafer Iscan, Gopalkumar Rakesh, Samantha Rossano, Jie Yang, Mengru Zhang, Jeffrey Miller, Gregory M Sullivan, Priya Sharma, Matthew McClure, Maria A Oquendo, J John Mann, Ramin V Parsey, Christine DeLorenzo
Symptoms of anxiety are highly comorbid with major depressive disorder (MDD) and are known to alter the course of the disease. To help elucidate the biological underpinnings of these prevalent disorders, we previously examined the relationship between components of anxiety (somatic, psychic and motoric) and serotonin 1A receptor (5-HT1A) binding in MDD and found that higher psychic and lower somatic anxiety was associated with greater 5-HT1A binding. In this work, we sought to examine the correlation between these anxiety symptom dimensions and 5-HTT binding...
August 12, 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28796086/sensitivity-and-specificity-of-clinical-and-laboratory-otolith-function-tests
#17
Lokesh Kumar, Alok Thakar, Bhaskar Thakur, Kapil Sikka
OBJECTIVE: To evaluate clinic based and laboratory tests of otolith function for their sensitivity and specificity in demarcating unilateral compensated complete vestibular deficit from normal. STUDY DESIGN: Prospective cross-sectional study. SETTING: Tertiary care hospital vestibular physiology laboratory. SUBJECTS: Control group-30 healthy adults, 20-45 years age; Case group-15 subjects post vestibular shwannoma excision or post-labyrinthectomy with compensated unilateral complete audio-vestibular loss...
October 2017: Otology & Neurotology
https://www.readbyqxmd.com/read/28792249/induced-neural-stem-cells-as-a-means-of-treatment-in-huntington-s-disease
#18
Kyung-Ah Choi, Sunghoi Hong
Huntington's disease (HD) is an inherited neurodegenerative disease characterized by chorea, dementia, and depression caused by progressive nerve cell degeneration, which is triggered by expanded CAG repeats in the huntingtin (Htt) gene. Currently, there is no cure for this disease, nor is there an effective medicine available to delay or improve the physical, mental, and behavioral severities caused by it. Areas covered: In this review, the authors describe the use of induced neural stem cells (iNSCs) by direct conversion technology, which offers great advantages as a therapeutic cell type to treat HD...
August 9, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28790887/mir-16-and-fluoxetine-both-reverse-autophagic-and-apoptotic-change-in-chronic-unpredictable-mild-stress-model-rats
#19
Yang Yang, Zhiying Hu, Xiaoxue Du, Henry Davies, Xue Huo, Marong Fang
In the clinic selective serotonin reuptake inhibitors (SSRIs), like Fluoxetine, remain the primary treatment for major depression. It has been suggested that miR-16 regulates serotonin transporters (SERT) via raphe nuclei and hippocampal responses to antidepressants. However, the underlying mechanism and regulatory pathways are still obtuse. Here, a chronic unpredicted mild stress (CUMS) depression model in rats was established, and then raphe nuclei miR-16 and intragastric Fluoxetine injections were administered for a duration of 3 weeks...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28789621/tics-as-an-initial-manifestation-of-juvenile-huntington-s-disease-case-report-and-literature-review
#20
Shi-Shuang Cui, Ru-Jing Ren, Ying Wang, Gang Wang, Sheng-Di Chen
BACKGROUND: Huntington's disease (HD) is an autosomal dominant disorder, typically characterized by chorea due to a trinucleotide repeat expansion in the HTT gene, although the clinical manifestations of patients with juvenile HD (JHD) are atypical. CASE PRESENTATION: A 17-year-old boy with initial presentation of tics attended our clinic and his DNA analysis demonstrated mutation in the HTT gene (49 CAG repeats). After treatment, his symptoms improved. Furthermore, we performed literature review through searching the databases and summarized clinical features in 33 JHD patients...
August 8, 2017: BMC Neurology
keyword
keyword
70418
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"