12,366 results match your criteria Huntington Disease Dementia


Peptidyl inhibition of Spt4-Spt5: Protein-protein inhibitors for targeting the transcriptional pathway related to C9orf72 expansion repeats.

J Cell Biochem 2020 Jul 6. Epub 2020 Jul 6.

Enamine Ltd., Kyiv, Ukraine.

Spt4/Spt5 is an useful target as it is likely a transcription factor that has implications for long non-coding RNA repeats related to frontotemporal dementia (FTD) found in the C9orf72 disease pathology. Inhibitors for Spt4/Spt5 using peptides as a starting point for assays as a means for developing small molecules, which could likely lead to therapeutic development for inhibition for Spt4/Spt5 with CNS characteristics. To elucidate the specific steps of identification and modification of key interacting residues from Spt4/Spt5 complex with further effect prediction, a set of different computational methods was applied. Read More

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http://dx.doi.org/10.1002/jcb.29820DOI Listing

Strategies for the molecular imaging of amyloid and the value of multi-modal approach.

ACS Sens 2020 Jul 5. Epub 2020 Jul 5.

Protein aggregation has been widely implicated in neurodegenerative diseases such as Alzheimer's disease (AD), frontotemporal dementia, Parkinson's disease and Huntington disease, as well as in systemic amyloidoses and conditions associated with localized amyloid deposits, such as type-II diabetes. The pressing need for a better understanding of the factors governing protein assembly has driven research for the development of molecular sensors for amyloidogenic proteins. To date, a number of sensors have been developed that report on the presence of protein aggregates utilizing various modalities, and their utility demonstrated for imaging protein aggregation in vitro and in vivo. Read More

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http://dx.doi.org/10.1021/acssensors.0c01101DOI Listing

Evaluating blood-brain barrier permeability in a rat model of type 2 diabetes.

J Transl Med 2020 Jun 24;18(1):256. Epub 2020 Jun 24.

Center for Translational NeuroImaging, Northeastern University, Boston, MA, USA.

Background: This is an exploratory study using a novel imaging modality, quantitative ultrashort time-to-echo, contrast enhanced (QUTE-CE) magnetic resonance imaging to evaluate the permeability of the blood-brain barrier in a rat model of type 2 diabetes with the presumption that small vessel disease is a contributing factor to neuropathology in diabetes.

Methods: The BBZDR/Wor rat, a model of type 2 diabetes, and age-matched controls were studied for changes in blood-brain barrier permeability. QUTE-CE, a quantitative vascular biomarker, generated angiographic images with over 500,000 voxels that were registered to a 3D MRI rat brain atlas providing site-specific information on blood-brain barrier permeability in 173 different brain areas. Read More

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http://dx.doi.org/10.1186/s12967-020-02428-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7313122PMC

[Huntington's disease and Sydenham's chorea].

Fortschr Neurol Psychiatr 2020 Jun 18;88(6):403-415. Epub 2020 Jun 18.

Huntington's disease was an important example for discussing the problem of predictive genetic testing. Like other movement disorders, it includes non-motor symptoms and a prodromal phase. As a rapidly progressive monogenetic disease, it is an important model disease for the study of neurodegenerative pathomechanisms and one of the first movement disorders for which causal therapies seem to be reachable. Read More

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http://dx.doi.org/10.1055/a-1124-0060DOI Listing

Restoration of CTSD (cathepsin D) and lysosomal function in stroke is neuroprotective.

Autophagy 2020 May 25:1-19. Epub 2020 May 25.

Department of Pharmacology and Toxicology, University of Alabama at Birmingham School of Medicine , Birmingham, AL, USA.

Stroke is a leading cause of death and disability. The pathophysiological mechanisms associated with stroke are very complex and not fully understood. Lysosomal function has a vital physiological function in the maintenance of cellular homeostasis. Read More

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http://dx.doi.org/10.1080/15548627.2020.1761219DOI Listing

Enhanced Clearance of Neurotoxic Misfolded Proteins by the Natural Compound Berberine and Its Derivatives.

Int J Mol Sci 2020 May 13;21(10). Epub 2020 May 13.

Dipartimento di Scienze Farmacologiche e Biomolecolari (DiSFeB), Dipartimento di Eccellenza 2018-2022, Centro di Eccellenza sulle Malattie Neurodegenerative, Università degli Studi di Milano, 20133 Milan, Italy.

Background: Accumulation of misfolded proteins is a common hallmark of several neurodegenerative disorders (NDs) which results from a failure or an impairment of the protein quality control (PQC) system. The PQC system is composed by chaperones and the degradative systems (proteasome and autophagy). Mutant proteins that misfold are potentially neurotoxic, thus strategies aimed at preventing their aggregation or at enhancing their clearance are emerging as interesting therapeutic targets for NDs. Read More

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http://dx.doi.org/10.3390/ijms21103443DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7279252PMC

APOE4 leads to blood-brain barrier dysfunction predicting cognitive decline.

Nature 2020 05 29;581(7806):71-76. Epub 2020 Apr 29.

Department of Physiology and Neuroscience, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.

Vascular contributions to dementia and Alzheimer's disease are increasingly recognized. Recent studies have suggested that breakdown of the blood-brain barrier (BBB) is an early biomarker of human cognitive dysfunction, including the early clinical stages of Alzheimer's disease. The E4 variant of apolipoprotein E (APOE4), the main susceptibility gene for Alzheimer's disease, leads to accelerated breakdown of the BBB and degeneration of brain capillary pericytes, which maintain BBB integrity. Read More

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http://dx.doi.org/10.1038/s41586-020-2247-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7250000PMC
May 2020
42.351 Impact Factor

ACR Appropriateness Criteria® Movement Disorders and Neurodegenerative Diseases.

J Am Coll Radiol 2020 May;17(5S):S175-S187

Specialty Chair, Atlanta VA Health Care System and Emory University, Atlanta, Georgia.

Movement disorders and neurodegenerative diseases are a variety of conditions that involve progressive neuronal degeneration, injury, or death. Establishing the correct diagnosis of a movement disorder or neurodegenerative process can be difficult due to the variable features of these conditions, unusual clinical presentations, and overlapping symptoms and characteristics. MRI has an important role in the initial assessment of these patients, although a combination of imaging and laboratory and genetic tests is often needed for complete evaluation and management. Read More

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http://dx.doi.org/10.1016/j.jacr.2020.01.042DOI Listing
May 2020
2.283 Impact Factor

The Role of the SLC Transporters Protein in the Neurodegenerative Disorders.

Clin Psychopharmacol Neurosci 2020 May;18(2):174-187

The solute carrier (SLC) superfamily is one of the major sub-groups of membrane proteins in mammalian cells. The solute carrier proteins include more than 400 different membrane-spanning solute carriers organized with 65 families in the human. In solute carrier family neurons, neurotransmitter is considered to be a pharmacological target of neuropsychiatric drugs because of their important role in the recovery of neurotransmitters such as GABA, glutamate, serotonin, dopamine and noradrenaline and regulation of their concentration in synaptic regions. Read More

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http://dx.doi.org/10.9758/cpn.2020.18.2.174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7236796PMC

MEF2 impairment underlies skeletal muscle atrophy in polyglutamine disease.

Acta Neuropathol 2020 Jul 18;140(1):63-80. Epub 2020 Apr 18.

Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, 48109, USA.

Polyglutamine (polyQ) tract expansion leads to proteotoxic misfolding and drives a family of nine diseases. We study spinal and bulbar muscular atrophy (SBMA), a progressive degenerative disorder of the neuromuscular system caused by the polyQ androgen receptor (AR). Using a knock-in mouse model of SBMA, AR113Q mice, we show that E3 ubiquitin ligases which are a hallmark of the canonical muscle atrophy machinery are not induced in AR113Q muscle. Read More

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http://dx.doi.org/10.1007/s00401-020-02156-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7166004PMC

PolyQ-independent toxicity associated with novel translational products from CAG repeat expansions.

PLoS One 2020 2;15(4):e0227464. Epub 2020 Apr 2.

Graduate Program in Cell Biology and Molecular Physiology, University of Pittsburgh Medical Center, Pittsburgh, PA, United States of America.

Expanded CAG nucleotide repeats are the underlying genetic cause of at least 14 incurable diseases, including Huntington's disease (HD). The toxicity associated with many CAG repeat expansions is thought to be due to the translation of the CAG repeat to create a polyQ protein, which forms toxic oligomers and aggregates. However, recent studies show that HD CAG repeats undergo a non-canonical form of translation called Repeat-associated non-AUG dependent (RAN) translation. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0227464PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7117740PMC

Antisense oligonucleotides for neurodegeneration.

Science 2020 Mar;367(6485):1428-1429

Huntington's Disease Centre, Department of Neurodegenerative Disease, and UK Dementia Research Institute at UCL, UCL Queen Square Institute of Neurology, University College London, London, UK.

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http://dx.doi.org/10.1126/science.aba4624DOI Listing

Protein transmission in neurodegenerative disease.

Nat Rev Neurol 2020 04 23;16(4):199-212. Epub 2020 Mar 23.

The Department of Pathology and Laboratory Medicine, Institute on Aging and Center for Neurodegenerative Disease Research, The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.

Most neurodegenerative diseases are characterized by the intracellular or extracellular aggregation of misfolded proteins such as amyloid-β and tau in Alzheimer disease, α-synuclein in Parkinson disease, and TAR DNA-binding protein 43 in amyotrophic lateral sclerosis. Accumulating evidence from both human studies and disease models indicates that intercellular transmission and the subsequent templated amplification of these misfolded proteins are involved in the onset and progression of various neurodegenerative diseases. The misfolded proteins that are transferred between cells are referred to as 'pathological seeds'. Read More

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http://dx.doi.org/10.1038/s41582-020-0333-7DOI Listing

Mild cognitive impairment in Huntington's disease?

Authors:
Emilia J Sitek

J Neurol Sci 2020 Jun 16;413:116779. Epub 2020 Mar 16.

Neurological and Psychiatric Nursing Department, Faculty of Health Sciences, Medical University of Gdansk, ul. Sklodowskiej-Curie 3a, Gdansk, Poland; Neurology Department, St. Adalbert Hospital, Copernicus PL, Al. Jana Pawla II 50, Gdansk, Poland; ENROLL-HD Study Site, St. Adalbert Hospital, Copernicus PL, Gdansk, Poland. Electronic address:

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http://dx.doi.org/10.1016/j.jns.2020.116779DOI Listing

A comparison between the neurocognitive profile of Huntington Disease-Like 2 and Huntington Disease: Exploring the presence of double dissociations.

Appl Neuropsychol Adult 2020 Mar 9:1-11. Epub 2020 Mar 9.

Division of Human Genetics, National Health Laboratory Service and School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.

Huntington Disease Like-2 (HDL2) is a rare autosomal dominant genetic disease caused by a mutation in the JPH3 gene. HDL2 is the Huntington Disease (HD) phenocopy that has the greatest clinical resemblance to HD. Both are characterized by movement, psychiatric and cognitive dysfunction, which progress to dementia. Read More

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http://dx.doi.org/10.1080/23279095.2020.1734810DOI Listing

Judgment in ABC case rules on confidentiality.

Authors:
Jacqui Thornton

Lancet 2020 03;395(10226):771-772

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http://dx.doi.org/10.1016/S0140-6736(20)30494-3DOI Listing

The discriminative capacity of CSF β-amyloid 42 and Tau in neurodegenerative diseases in the Chinese population.

J Neurol Sci 2020 May 22;412:116756. Epub 2020 Feb 22.

Department of Neurology and Research Center of Neurology in Second Affiliated Hospital, Key Laboratory of Medical Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, China; CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai, China. Electronic address:

Introduction: In the past few years, the β-amyloid 42 peptide and tau protein in cerebrospinal fluid (CSF) have become primary diagnostic biomarkers in differentiating Alzheimer's disease (AD) and cognitive normal controls. As we know, several neurodegenerative diseases have been reported to overlap with AD in neuropathology and clinical symptoms. To examine the discriminative utility of these biomarkers in AD and other neurodegenerative diseases, we measured them in a cohort of Chinese population. Read More

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http://dx.doi.org/10.1016/j.jns.2020.116756DOI Listing

Abrogation of prenucleation, transient oligomerization of the Huntingtin exon 1 protein by human profilin I.

Proc Natl Acad Sci U S A 2020 03 3;117(11):5844-5852. Epub 2020 Mar 3.

Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0520;

Human profilin I reduces aggregation and concomitant toxicity of the polyglutamine-containing N-terminal region of the huntingtin protein encoded by exon 1 (htt) and responsible for Huntington's disease. Here, we investigate the interaction of profilin with htt using NMR techniques designed to quantitatively analyze the kinetics and equilibria of chemical exchange at atomic resolution, including relaxation dispersion, exchange-induced shifts, and lifetime line broadening. We first show that the presence of two polyproline tracts in htt, absent from a shorter huntingtin variant studied previously, modulates the kinetics of the transient branched oligomerization pathway that precedes nucleation, resulting in an increase in the populations of the on-pathway helical coiled-coil dimeric and tetrameric species (τ ≤ 50 to 70 μs), while leaving the population of the off-pathway (nonproductive) dimeric species largely unaffected (τ ∼750 μs). Read More

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http://dx.doi.org/10.1073/pnas.1922264117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7084121PMC

Gene therapy conversion of striatal astrocytes into GABAergic neurons in mouse models of Huntington's disease.

Nat Commun 2020 02 27;11(1):1105. Epub 2020 Feb 27.

Department of Biology, Huck Institutes of Life Sciences, Pennsylvania State University, University Park, PA, 16802, USA.

Huntington's disease (HD) is caused by Huntingtin (Htt) gene mutation resulting in the loss of striatal GABAergic neurons and motor functional deficits. We report here an in vivo cell conversion technology to reprogram striatal astrocytes into GABAergic neurons in both R6/2 and YAC128 HD mouse models through AAV-mediated ectopic expression of NeuroD1 and Dlx2 transcription factors. We found that the astrocyte-to-neuron (AtN) conversion rate reached 80% in the striatum and >50% of the converted neurons were DARPP32 medium spiny neurons. Read More

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http://dx.doi.org/10.1038/s41467-020-14855-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7046613PMC
February 2020

Measuring the quality of care in nursing home residents with early-onset neurodegenerative diseases: a scoping review.

BMC Palliat Care 2020 Feb 27;19(1):25. Epub 2020 Feb 27.

Department of Health Services Research and Care and Public Health Research Institute (CAPHRI), Maastricht University, Maastricht, The Netherlands.

Background: Nursing home residents with early-onset neurodegenerative diseases are often younger in comparison with other residents, and need different, often more complex care. Accordingly, the measurements currently used for measuring quality of care in nursing homes may not be suitable for use in this target group. Little is known about the experiences of these residents and of their (in) formal caregivers regarding the quality of care they receive. Read More

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http://dx.doi.org/10.1186/s12904-020-0528-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7047396PMC
February 2020

Combining feature selection and shape analysis uncovers precise rules for miRNA regulation in Huntington's disease mice.

BMC Bioinformatics 2020 Feb 24;21(1):75. Epub 2020 Feb 24.

Sorbonne Université, CNRS UMR8256, INSERM ERL U1164, Brain-C Lab, Paris, France.

Background: MicroRNA (miRNA) regulation is associated with several diseases, including neurodegenerative diseases. Several approaches can be used for modeling miRNA regulation. However, their precision may be limited for analyzing multidimensional data. Read More

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http://dx.doi.org/10.1186/s12859-020-3418-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7041117PMC
February 2020

A slipped-CAG DNA-binding small molecule induces trinucleotide-repeat contractions in vivo.

Nat Genet 2020 02 14;52(2):146-159. Epub 2020 Feb 14.

Program of Genetics & Genome Biology, The Hospital for Sick Children, The Peter Gilgan Centre for Research and Learning, Toronto, Ontario, Canada.

In many repeat diseases, such as Huntington's disease (HD), ongoing repeat expansions in affected tissues contribute to disease onset, progression and severity. Inducing contractions of expanded repeats by exogenous agents is not yet possible. Traditional approaches would target proteins driving repeat mutations. Read More

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http://dx.doi.org/10.1038/s41588-019-0575-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7043212PMC
February 2020

Hung-up Knee Jerk in Huntington's Disease.

N Engl J Med 2020 Feb;382(7):e10

University of Tokushima, Tokushima, Japan

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http://dx.doi.org/10.1056/NEJMicm1910309DOI Listing
February 2020

Basal ganglia role in learning rewarded actions and executing previously learned choices: Healthy and diseased states.

PLoS One 2020 10;15(2):e0228081. Epub 2020 Feb 10.

Indiana Alcohol Research Center, IUSM, Indianapolis, Indiana, United States of America.

The basal ganglia (BG) is a collection of nuclei located deep beneath the cerebral cortex that is involved in learning and selection of rewarded actions. Here, we analyzed BG mechanisms that enable these functions. We implemented a rate model of a BG-thalamo-cortical loop and simulated its performance in a standard action selection task. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0228081PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7010262PMC

Utility of the Parkinson's disease-Cognitive Rating Scale for the screening of global cognitive status in Huntington's disease.

J Neurol 2020 May 7;267(5):1527-1535. Epub 2020 Feb 7.

Movement Disorders Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau, Mas Casanovas 90, 08041, Barcelona, Spain.

Background: Cognitive impairment is an essential feature of Huntington's disease (HD) and dementia is a predictable outcome in all patients. However, validated instruments to assess global cognitive performance in the field of HD are lacking.

Objectives: We aimed to explore the utility of the Parkinson's disease-Cognitive Rating Scale (PD-CRS) for the screening of global cognition in HD. Read More

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http://dx.doi.org/10.1007/s00415-020-09730-6DOI Listing

Investigating RNA editing in deep transcriptome datasets with REDItools and REDIportal.

Nat Protoc 2020 03 29;15(3):1098-1131. Epub 2020 Jan 29.

Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies (IBIOM), National Research Council, Bari, Italy.

RNA editing is a widespread post-transcriptional mechanism able to modify transcripts through insertions/deletions or base substitutions. It is prominent in mammals, in which millions of adenosines are deaminated to inosines by members of the ADAR family of enzymes. A-to-I RNA editing has a plethora of biological functions, but its detection in large-scale transcriptome datasets is still an unsolved computational task. Read More

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http://dx.doi.org/10.1038/s41596-019-0279-7DOI Listing

Blood and brain gene expression trajectories mirror neuropathology and clinical deterioration in neurodegeneration.

Brain 2020 02;143(2):661-673

McConnell Brain Imaging Center, Montreal Neurological Institute, Montreal, Canada.

Most prevalent neurodegenerative disorders take decades to develop and their early detection is challenged by confounding non-pathological ageing processes. For all neurodegenerative conditions, we continue to lack longitudinal gene expression data covering their large temporal evolution, which hinders the understanding of the underlying dynamic molecular mechanisms. Here, we overcome this key limitation by introducing a novel gene expression contrastive trajectory inference (GE-cTI) method that reveals enriched temporal patterns in a diseased population. Read More

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http://dx.doi.org/10.1093/brain/awz400DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7009530PMC
February 2020

IFNB/interferon-β regulates autophagy via a -TBC1D15-RAB7 pathway.

Autophagy 2020 04 20;16(4):767-769. Epub 2020 Jan 20.

Development and Stem Cells Program, Monash Biomedicine Discovery Institute and Department of Anatomy and Developmental Biology, Monash University, Melbourne, Australia.

Loss of IFNB/interferon-β in mice causes a Parkinson disease-like phenotype where many features, including SNCA/α-synuclein and MAPT/tau accumulation, can be attributed to a late-stage block in autophagic flux. Recently, we identified a mechanism that can explain this phenotype. We found that IFNB induces expression of , a microRNA that can reduce the levels of TBC1D15, a RAB GTPase-activating protein. Read More

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http://dx.doi.org/10.1080/15548627.2020.1718384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7138209PMC

Altered Cortical Morphometry in Pre-manifest Huntington's Disease: Cross-sectional Data from the IMAGE-HD Study.

Conf Proc IEEE Eng Med Biol Soc 2019 07;2019:2844-2847

Huntington's disease (HD) is an inherited progressive neurodegenerative disease mainly associated with subcortical striatal atrophy. There is also strong evidence showing cerebral atrophy and cortical thinning; however, limited research has investigated altered patterns of cortical folding in this disease. Here, we investigated cortical morphometry via both gyrification index (GI, a measure of cortical folding) and cortical thinning. Read More

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http://dx.doi.org/10.1109/EMBC.2019.8857240DOI Listing

Neuroendocrine Disturbances in Neurodegenerative Disorders: A Scoping Review.

Psychosomatics 2020 Mar - Apr;61(2):105-115. Epub 2019 Nov 15.

Harvard Medical School, Boston, MA; Departments of Psychiatry and Neurology, Massachusetts General Hospital/Harvard Medical School, Boston, MA.

Background: Neurodegenerative diseases cause progressive irreversible neuronal loss that has broad downstream effects. The neuroendocrine system regulates homeostasis of circuits that control critical functions such as the stress response, metabolism, reproduction, fluid balance, and glucose control. These systems are frequently disrupted in neurodegenerative disorders yet often overlooked in clinical practice. Read More

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http://dx.doi.org/10.1016/j.psym.2019.11.002DOI Listing
November 2019

Bioinformatics analysis of the molecular mechanism underlying Huntington's disease.

J Integr Neurosci 2019 Dec;18(4):369-376

Department of Neurology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P. R. China.

We explore the underlying molecular mechanisms and to identify key molecules in Huntington's disease by utilizing bioinformatics methods. The gene expression profile of GSE3621 was extracted from the gene expression omnibus. Differentially expressed genes between the R6/1 transgenic mouse model of Huntington's disease and controls at different time points were screened by limma package in R. Read More

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http://dx.doi.org/10.31083/j.jin.2019.04.1176DOI Listing
December 2019

The effects of dual-task cognitive interference on gait and turning in Huntington's disease.

PLoS One 2020 7;15(1):e0226827. Epub 2020 Jan 7.

Department of Cell and Molecular Medicine, Rush University Medical Center, Chicago, IL, United States of America.

Huntington's disease (HD) is characterized by motor, cognitive, and psychiatric dysfunction. HD progression causes loss of automaticity, such that previously automatic tasks require greater attentional resources. Dual-task (DT) paradigms and fast-paced gait may stress the locomotor system, revealing deficits not seen under single-task (ST). Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0226827PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6946131PMC

Clinical recommendations to guide physical therapy practice for Huntington disease.

Neurology 2020 02 6;94(5):217-228. Epub 2020 Jan 6.

From the Department of Biobehavioral Sciences (L.Q.), Teachers College, Columbia University, New York, NY; Physical Therapy Division (D.K., A.K.), School of Health and Rehabilitation Sciences, The Ohio State University, Columbus; Program in Physical Therapy (A.K.R.), Department of Rehabilitative and Regenerative Medicine, G.H. Sergievsky Center, Columbia University, New York, NY; Centre for Trials Research (M.B.), College of Biomedical and Life Sciences, Cardiff University, United Kingdom; and Program in Physical Therapy (N.E.F.), Wayne State University, Detroit, MI.

Objective: In the past decade, an increasing number of studies have examined the efficacy of physical therapy interventions in people with Huntington disease (HD).

Methods: We performed a mixed-methods systematic review using Joanna Briggs Institute (JBI) methodology and included experimental and observational study designs. The search resulted in 23 quantitative studies and 3 qualitative studies from which we extracted data using JBI standardized extraction tools. Read More

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http://dx.doi.org/10.1212/WNL.0000000000008887DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7080285PMC
February 2020

Huntington's Disease Pathogenesis Is Modified In Vivo by Alfy/Wdfy3 and Selective Macroautophagy.

Neuron 2020 03 30;105(5):813-821.e6. Epub 2019 Dec 30.

Doctoral Program in Neurobiology and Behavior, Department of Neuroscience, Columbia University, New York, NY, USA; Department of Neurology, Columbia University, New York, NY, USA; Department of Pathology and Cell Biology, Columbia University, New York, NY, USA. Electronic address:

Despite being an autosomal dominant disorder caused by a known coding mutation in the gene HTT, Huntington's disease (HD) patients with similar trinucleotide repeat mutations can have an age of onset that varies by decades. One likely contributing factor is the genetic heterogeneity of patients that might modify their vulnerability to disease. We report that although the heterozygous depletion of the autophagy adaptor protein Alfy/Wdfy3 has no consequence in control mice, it significantly accelerates age of onset and progression of HD pathogenesis. Read More

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http://dx.doi.org/10.1016/j.neuron.2019.12.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7060123PMC

Economic burden of Huntington's disease in Peru.

BMC Health Serv Res 2019 Dec 30;19(1):1017. Epub 2019 Dec 30.

Neurogenetics Research Center, Instituto Nacional de Ciencias Neurológicas, 1271 Ancash St, 15003, Lima, Peru.

Background: Huntington's disease (HD) is a devastating and fatal neurodegenerative disorder that leads to progressive disability, and over time to total dependence. The economic impact of HD on patients living in developing countries like Peru is still unknown. This study aims to estimate the economic burden by estimating direct and indirect costs of Huntington's disease in Peru, as well as the proportion of direct costs borne by patients and their families. Read More

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http://dx.doi.org/10.1186/s12913-019-4806-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6937635PMC
December 2019

[The Role of Mutant RNA in the Pathogenesis of Huntington's Disease and Other Polyglutamine Diseases].

Mol Biol (Mosk) 2019 Nov-Dec;53(6):954-967

Federal Research and Clinical Center of Physical-Chemical Medicine, Federal Medical Biological Agency, Moscow, 119435 Russia.

Polyglutamine diseases are rare, inherited neurodegenerative pathologies that arise as a result of expansion of trinucleotide CAG repeats in the coding segment of certain genes. This expansion leads to the appearance of mRNA with abnormally long repetitive CAG triplets (mCAG-RNA) and proteins with polyglutamine (PolyQ) tracts in the cells, which is why these pathologies are commonly termed polyglutamine diseases, or PolyQ diseases. To date, nine PolyQ diseases have been described: Huntington's disease, dentatorubral pallidoluysian atrophy (DRPLA), spinal and bulbar muscular atrophy (SBMA), and six different types of spinocerebellar ataxia (SCA 1,2,3,6,7, and 17). Read More

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http://dx.doi.org/10.1134/S002689841906003XDOI Listing
January 2020

Chorea-related mutations in PDE10A result in aberrant compartmentalization and functionality of the enzyme.

Proc Natl Acad Sci U S A 2020 01 23;117(1):677-688. Epub 2019 Dec 23.

Institute of Cardiovascular and Medical Science, University of Glasgow, G12 8QQ Glasgow, United Kingdom;

A robust body of evidence supports the concept that phosphodiesterase 10A (PDE10A) activity in the basal ganglia orchestrates the control of coordinated movement in human subjects. Although human mutations in the PDE10A gene manifest in hyperkinetic movement disorders that phenocopy many features of early Huntington's disease, characterization of the maladapted molecular mechanisms and aberrant signaling processes that underpin these conditions remains scarce. Recessive mutations in the GAF-A domain have been shown to impair PDE10A function due to the loss of striatal PDE10A protein levels, but here we show that this paucity is caused by irregular intracellular trafficking and increased PDE10A degradation in the cytosolic compartment. Read More

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http://dx.doi.org/10.1073/pnas.1916398117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6955301PMC
January 2020

Paraneoplastic Chorea Managed with Intravenous Amantadine.

Tremor Other Hyperkinet Mov (N Y) 2019 2;9. Epub 2019 Dec 2.

Department of Neurology, Kansas University Medical Center, Kansas City, KS, USA.

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http://dx.doi.org/10.7916/tohm.v0.743DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6898895PMC

[Anti-sense oligonucleotides RNA therapy in Huntington disease: a great promise and many unknowns].

Authors:
Alexandra Durr

Med Sci (Paris) 2019 Nov 17;35(11):834-836. Epub 2019 Dec 17.

Sorbonne Université, Institut du cerveau et de la moelle épinière (ICM), AP-HP, Inserm, CNRS, Hôpital Pitié-Salpêtrière, 47-83 boulevard de l'Hôpital, 75013 Paris, France.

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http://dx.doi.org/10.1051/medsci/2019165DOI Listing
November 2019

Targeting N-Terminal Huntingtin with a Dual-sgRNA Strategy by CRISPR/Cas9.

Biomed Res Int 2019 16;2019:1039623. Epub 2019 Nov 16.

Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA.

Huntington's disease (HD) is an autosomal dominant progressive neurodegenerative disorder, caused by a CAG/polyglutamine (polyQ) repeat expansion in the (HTT) gene. The polyQ tract is located in and transcribed from N-terminal HTT of exon 1. HTT is a large multifaceted protein, which participates in a range of cellular functions. Read More

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http://dx.doi.org/10.1155/2019/1039623DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6881766PMC

Epidemiology and health care utilization of patients suffering from Huntington's disease in Germany: real world evidence based on German claims data.

BMC Neurol 2019 Dec 10;19(1):318. Epub 2019 Dec 10.

IGES Institut GmbH, Friedrichstraße 180, 10117, Berlin, Germany.

Background: Huntington's disease (HD) is a rare, genetic, neurodegenerative and ultimately fatal disease with no cure or progression-delaying treatment currently available. HD is characterized by a triad of cognitive, behavioural and motor symptoms. Evidence on epidemiology and management of HD is limited, especially for Germany. Read More

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http://dx.doi.org/10.1186/s12883-019-1556-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6905058PMC
December 2019

Pupillometry evaluation of melanopsin retinal ganglion cell function and sleep-wake activity in pre-symptomatic Alzheimer's disease.

PLoS One 2019 10;14(12):e0226197. Epub 2019 Dec 10.

Doheny Eye institute, UCLA Stein Eye Institute, University of California, Los Angeles, Department of Ophthalmology, Los Angeles, California, United States of America.

Background: Melanopsin-expressing retinal ganglion cells (mRGCs), intrinsically photosensitive RGCs, mediate the light-based pupil response and the light entrainment of the body's circadian rhythms through their connection to the pretectal nucleus and hypothalamus, respectively. Increased awareness of circadian rhythm dysfunction in neurological conditions including Alzheimer's disease (AD), has led to a wave of research focusing on the role of mRGCs in these diseases. Postmortem retinal analyses in AD patients demonstrated a significant loss of mRGCs, and in vivo measurements of mRGC function with chromatic pupillometry may be a potential biomarker for early diagnosis and progression of AD. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0226197PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6903762PMC

Therapeutic Antisense Targeting of Huntingtin.

DNA Cell Biol 2020 Feb 10;39(2):154-158. Epub 2019 Dec 10.

Huntington's Disease Centre, Department of Neurodegenerative Disease, University College London (UCL) Queen Square Institute of Neurology, and the UK Dementia Research Institute at UCL, London, United Kingdom.

Antisense oligonucleotides (ASOs) are a relatively new therapeutic entity that utilizes short chemically modified strands of DNA in targeted interactions with RNA to modulate the type or amount of resultant protein. This brief review summarizes the preclinical, translational, and early clinical development of an ASO designed to reduce the production of the disease-causing protein in Huntington's disease, an inherited neurodegenerative disease. Read More

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http://dx.doi.org/10.1089/dna.2019.5188DOI Listing
February 2020

Autoregressive modeling to assess stride time pattern stability in individuals with Huntington's disease.

BMC Neurol 2019 Dec 9;19(1):316. Epub 2019 Dec 9.

Biomedical Engineering, School of Engineering, University of Connecticut, 260 Glenbrook Road, Storrs, CT, 06269-3247, USA.

Background: Huntington's disease (HD) is a progressive, neurological disorder that results in both cognitive and physical impairments. These impairments affect an individual's gait and, as the disease progresses, it significantly alters one's stability. Previous research found that changes in stride time patterns can help delineate between healthy and pathological gait. Read More

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http://dx.doi.org/10.1186/s12883-019-1545-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6902547PMC
December 2019

TRPC5 channel instability induced by depalmitoylation protects striatal neurons against oxidative stress in Huntington's disease.

Biochim Biophys Acta Mol Cell Res 2020 02 6;1867(2):118620. Epub 2019 Dec 6.

Department of Physiology and Institute of Dermatological Science, Seoul National University College of Medicine, Seoul 03080, South Korea. Electronic address:

Protein S-palmitoylation, the covalent lipid modification of the side chain of Cys residues with the 16‑carbon fatty acid palmitate, is the most common acylation, and it enhances the membrane stability of ion channels. This post-translational modification (PTM) determines a functional mechanism of ion channel life cycle from maturation and membrane trafficking to localization. Especially, neurodevelopment is regulated by balancing the level of synaptic protein palmitoylation/depalmitoylation. Read More

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http://dx.doi.org/10.1016/j.bbamcr.2019.118620DOI Listing
February 2020

Interplay between MicroRNAs and Oxidative Stress in Neurodegenerative Diseases.

Int J Mol Sci 2019 Nov 30;20(23). Epub 2019 Nov 30.

Institute of Biotechnology, HiLIFE, University of Helsinki, 00014 Helsinki, Finland.

MicroRNAs are post-transcriptional regulators of gene expression, crucial for neuronal differentiation, survival, and activity. Age-related dysregulation of microRNA biogenesis increases neuronal vulnerability to cellular stress and may contribute to the development and progression of neurodegenerative diseases. All major neurodegenerative disorders are also associated with oxidative stress, which is widely recognized as a potential target for protective therapies. Read More

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http://dx.doi.org/10.3390/ijms20236055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6929013PMC
November 2019