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Samina Salim
Biochemical integrity of the brain is vital for normal functioning of the central nervous system (CNS). One of the contributing factors of cerebral biochemical impairment is a chemical process called oxidative stress. Oxidative stress occurs upon excessive free radical production due to insufficiency of counteracting antioxidant response system. The brain with its high oxygen consumption and lipid-rich content is highly susceptible to oxidative stress. Therefore, oxidative stress-induced damage to the brain has a strong potential to negatively impact normal CNS functions...
October 17, 2016: Journal of Pharmacology and Experimental Therapeutics
João Casaca-Carreira, Yasin Temel, Iñaki Larrakoetxea, Ali Jahanshahi
Antisense oligonucleotide (AON) therapy is emerging as a potential treatment strategy for neurodegenerative diseases, such as spinal muscular atrophy, Huntington's disease, and amyotrophic lateral sclerosis. AONs function at the cellular level by, for example, direct interference with the expression of gene products or the molecular activation of neuroprotective pathways. However, AON therapy faces a major obstacle limiting its clinical application for central nervous system (CNS) disorders: the blood-brain barrier...
October 18, 2016: Nucleic Acid Therapeutics
David Mathar, Leonora Wilkinson, Anna K Holl, Jane Neumann, Lorenz Deserno, Arno Villringer, Marjan Jahanshahi, Annette Horstmann
Incidental learning of appropriate stimulus-response associations is crucial for optimal functioning within our complex environment. Positive and negative prediction errors (PEs) serve as neural teaching signals within distinct ('direct'/'indirect') dopaminergic pathways to update associations and optimize subsequent behavior. Using a computational reinforcement learning model, we assessed learning from positive and negative PEs on a probabilistic task (Weather Prediction Task - WPT) in three populations that allow different inferences on the role of dopamine (DA) signals: (1) Healthy volunteers that repeatedly underwent [(11)C]raclopride Positron Emission Tomography (PET), allowing for assessment of striatal DA release during learning, (2) Parkinson's disease (PD) patients tested both on and off L-DOPA medication, (3) early Huntington's disease (HD) patients, a disease that is associated with hyper-activation of the 'direct' pathway...
September 19, 2016: Cortex; a Journal Devoted to the Study of the Nervous System and Behavior
Koning Shen, Barbara Calamini, Jonathan A Fauerbach, Boxue Ma, Sarah H Shahmoradian, Ivana L Serrano Lachapel, Wah Chiu, Donald C Lo, Judith Frydman
Many neurodegenerative diseases are linked to amyloid aggregation. In Huntington's disease (HD), neurotoxicity correlates with increased aggregation propensity of a polyglutamine (polyQ) expansion in exon 1 of mutant huntingtin protein (mHtt). Here we establish how the domains flanking the polyQ tract shape the mHtt conformational landscape in vitro and in neurons. In vitro, the flanking domains have opposing effects on the conformation and stabilities of oligomers and amyloid fibrils. The N-terminal N17 promotes amyloid fibril formation, while the C-terminal Proline Rich Domain destabilizes fibrils and enhances oligomer formation...
October 18, 2016: ELife
Ralf Reilmann
No abstract text is available yet for this article.
October 17, 2016: JAMA Neurology
Russell L Margolis, Dobrila D Rudnicki
PURPOSE OF REVIEW: Huntington's disease-like 2 (HDL2) is a rare, progressive, autosomal dominant neurodegenerative disorder that genetically, clinically, and pathologically closely resembles Huntington's disease. We review HDL2 pathogenic mechanisms and examine the implications of these mechanisms for Huntington's disease and related diseases. RECENT FINDINGS: HDL2 is caused by a CTG/CAG repeat expansion in junctophilin-3. Available data from cell and animal models and human brain suggest that HDL2 is a complex disease in which transcripts and proteins expressed bidirectionally from the junctophilin-3 locus contribute to pathogenesis through both gain-and loss-of-function mechanisms...
October 5, 2016: Current Opinion in Neurology
Sebastian Frese, Jens A Petersen, Maria Ligon-Auer, Sandro Manuel Mueller, Violeta Mihaylova, Saskia M Gehrig, Veronika Kana, Elisabeth J Rushing, Evelyn Unterburger, Georg Kägi, Jean-Marc Burgunder, Marco Toigo, Hans H Jung
Huntington disease (HD) is a relentlessly progressive neurodegenerative disorder with symptoms across a wide range of neurological domains, including cognitive and motor dysfunction. There is still no causative treatment for HD but environmental factors such as passive lifestyle may modulate disease onset and progression. In humans, multidisciplinary rehabilitation has a positive impact on cognitive functions. However, a specific role for exercise as a component of an environmental enrichment effect has been difficult to demonstrate...
October 17, 2016: Journal of Neurology
Mark B Warren, Kathryn M Schak
A diagnosis of Huntington's disease has broad social, vocational, reproductive and psychological implications. The ability to accurately diagnose the illness via genetic testing is not new. However, given a persistent lack of robustly effective interventions, it remains an area of ethical concern. The difficulty is compounded in cases of intellectual disability. This paper presents a case of genetic testing for Huntington's disease conducted on a patient with intellectual disability with guardian consent, but without the patient's direct knowledge and how the family illness narrative and psychiatric care were employed in the eventual disclosure of the patient's diagnosis and subsequent management...
October 15, 2016: Journal of Genetic Counseling
John S Bett
Cells have developed an evolutionary obligation to survey and maintain proteome fidelity and avoid the possible toxic consequences of protein misfolding and aggregation. Disturbances to protein homoeostasis (proteostasis) can result in severe cellular phenotypes and are closely linked with the accumulation of microscopically visible deposits of aggregated proteins. These include inclusion bodies found in AD (Alzheimer's disease), HD (Huntington's disease) and ALS (amyotrophic lateral sclerosis) patient neurons...
October 15, 2016: Essays in Biochemistry
S F Huntington
No abstract text is available yet for this article.
October 13, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Kimberly A Quaid, Shirley W Eberly, Elise Kayson-Rubin, David Oakes, Ira Shoulson
Huntington disease (HD) is a late onset ultimately fatal neurodegenerative disorder caused by a CAG triplet repeat expansion in the Huntingtin gene which was discovered in 1993. The PHAROS study is a unique observational study of 1001 individuals at risk for HD who had not been previously tested for HD and who had no plans to do so. In this cohort, 104 (10%) individuals changed their minds and chose to be tested during the course of the study but outside of the study protocol. Baseline behavioral scores, especially apathy, were more strongly associated with later genetic testing than motor and chorea scores, particularly among subjects with expanded CAG repeat length...
October 14, 2016: Clinical Genetics
Yoshihiro Kino, Chika Washizu, Masaru Kurosawa, Mizuki Yamada, Hiroshi Doi, Toru Takumi, Hiroaki Adachi, Masahisa Katsuno, Gen Sobue, Geoffrey G Hicks, Nobutaka Hattori, Tomomi Shimogori, Nobuyuki Nukina
FUS/TLS is an RNA/DNA-binding protein associated with neurodegenerative diseases including amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Previously, we found that a prion-like domain in the N-terminus of FUS/TLS mediates co-aggregation between FUS/TLS and mutant huntingtin, the gene product of Huntington's disease (HD). Here, we show that heterozygous knockout of FUS/TLS worsened the phenotypes of model mice of (HD, but not spinal and bulbar muscular atrophy (SBMA). This difference was correlated with the degree of pathological association between disease proteins and FUS/TLS...
October 14, 2016: Scientific Reports
Yuwei Jiang, Sonja E DiGregorio, Martin L Duennwald, Patrick Lajoie
The palette of fluorescent proteins (FPs) available for live-cell imaging contains proteins that strongly differ in their biophysical properties. FPs cannot be assumed to be equivalent and in certain cases could significantly perturb the behavior of fluorescent reporters. We employed Saccharomyces cerevisiae to comprehensively study the impact of FPs on the toxicity of polyglutamine (polyQ) expansion proteins associated with Huntington's disease. The toxicity of polyQ fusion constructs is highly dependent on the sequences flanking the polyQ repeats...
October 13, 2016: Traffic
Chiara Sarappa, Elena Salvatore, Alessandro Filla, Sirio Cocozza, Cinzia Valeria Russo, Francesco Saccà, Arturo Brunetti, Giuseppe De Michele, Mario Quarantelli
The fractional Amplitude of Low Frequency Fluctuations (fALFF) and the degree of local synchronization (Regional Homogeneity - ReHo) of resting-state BOLD signal have been suggested to map spontaneous neuronal activity and local functional connectivity, respectively. We compared voxelwise, independent of atrophy, the fALFF and ReHo patterns of 11 presymptomatic (ps-HD) and 28 symptomatic (sHD) Huntington's disease mutation carriers, with those of 40 normal volunteers, and tested their possible correlations with the motor and cognitive subscores of the Unified Huntington's Disease Rating Scale...
October 12, 2016: Brain Imaging and Behavior
Tua Vinther-Jensen, Lars Börnsen, Esben Budtz-Jørgensen, Cecilie Ammitzbøll, Ida U Larsen, Lena E Hjermind, Finn Sellebjerg, Jørgen E Nielsen
OBJECTIVE: To investigate CSF biomarkers of neuroinflammation and neurodegeneration in Huntington disease (HD) gene-expansion carriers compared to controls and to investigate these biomarkers in association with clinical HD rating scales and disease burden score. METHODS: We collected CSF from 32 premanifest and 48 manifest HD gene-expansion carriers and 24 gene-expansion negative at-risk controls. We examined biomarkers of neuroinflammation (matrix metalloproteinase 9, C-X-C motif chemokine 13, terminal complement complex, chitinase-3-like-protein 1 [CHI3L1], and osteopontin [OPN]) and neurodegeneration (microtubule-associated protein tau, neurofilament light polypeptide [NFL], and myelin basic protein [MBP])...
December 2016: Neurology® Neuroimmunology & Neuroinflammation
Anahita Brown, Katherine Sewell, Caroline A Fisher
AIMS AND OBJECTIVES: A systematic review of aggression in an inpatient Huntington's cohort examining rates, types and antecedents. BACKGROUND: Although the prevalence of aggression in Huntington's disease is high, research into this problematic behaviour has been limited. Few studies have investigated the nature of aggressive behaviour in Huntington's or antecedents that may contribute to its occurrence. DESIGN: A systematic, double coded, electronic medical file audit...
October 12, 2016: Journal of Clinical Nursing
Hosung Kim, Ji-Hoon Kim, Katherine L Possin, Joseph Winer, Michael D Geschwind, Duan Xu, Christopher P Hess
In patients with premotor Huntington's disease (pmHD), literature has reported decreases in caudate volume. However, the regional vulnerability of the caudate nucleus to pmHD remains to be clarified. We aimed to determine whether regional structural damage of the caudate nucleus was present in pmHD and was correlated with clinical profile using a surface-based morphometric technique applied to T1-weighted MRI. The study cohort consisted of 14 volunteers with genetically confirmed pmHD (6 males; 41.8 ± 13...
October 11, 2016: Brain Imaging and Behavior
Ivan Vorisek, Michael Syka, Lydia Vargova
Diffusion-weighted magnetic resonance (DW-MR) is an important diagnostic tool in Huntington disease (HD), a fatal hereditary neurodegenerative disorder. To clarify the nature of diffusivity changes in HD, we compared the apparent diffusion coefficient of water (ADCW ) acquired by DW-MR with extracellular space volume fraction α and tortuosity λ, measured by the iontophoretic method in the R6/2 mouse model of HD and in wild-type controls (WT). In anisotropic globus pallidus (GP), diffusion measurements were performed in the mediolateral (x), rostrocaudal (y), and ventrodorsal (z) axes...
October 11, 2016: Journal of Neuroscience Research
Justin T Huntington, Robert L Plews, Sara A Mansfield, Joseph M Drosdeck, David C Evans
There are many complications associated with the left ventricular assist devices (LVADs), including gastrointestinal bleeding (GIB). We present a case of a pseudo colonic mass visualized on colonoscopy during workup for GIB in an LVAD patient necessitating a right colectomy with final pathology negative for malignancy. A review of the literature in regards to the pathology, diagnosis, and treatment of this interesting condition is included.
July 2016: International Journal of Critical Illness and Injury Science
Navneet Kaur, Puneet Kumar, Sumit Jamwal, Rahul Deshmukh, Vinod Gauttam
BACKGROUND: Tetrabenazine (TBZ) is the only US Food and Drug Administration-approved drug for the treatment of chorea related to Huntington's disease and other hyperkinetic disorders. TBZ was first synthesized in 1950, and was then used for the treatment of psychosis. But later its potential in treating hyperkinetic disorders was proved by its ability to block vesicular monoamine transporters 2 and deplete monoamine stores. There is still lack of awareness about the therapeutic potential of this drug...
September 2016: Annals of Neurosciences
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