scholarly journals Huntington's disease-like phenotype due to trinucleotide repeat expansions in the TBP and JPH3 genes

Brain ◽  
2003 ◽  
Vol 126 (7) ◽  
pp. 1599-1603 ◽  
Author(s):  
G. Stevanin
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Trinucleotide Repeat ◽  
Repeat Expansions

Trinucleotide repeat expansions in thejunctophilin-3 gene are not found in caucasian patients with a huntington's disease-like phenotype

2002 ◽  
Vol 51 (5) ◽  
pp. 662-662 ◽  
Author(s):  
Ingrid Bauer ◽  
Martin Gencik ◽  
Franco Laccone ◽  
Hartmut Peters ◽  
Bernhard H. F. Weber ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Trinucleotide Repeat ◽  
Repeat Expansions ◽  
Caucasian Patients

scholarly journals RNA Sequencing of Human Peripheral Blood Cells Indicates Upregulation of Immune-Related Genes in Huntington's Disease

2020 ◽  
Vol 11 ◽  
Author(s):  
Miguel A. Andrade-Navarro ◽  
Katja Mühlenberg ◽  
Eike J. Spruth ◽  
Nancy Mah ◽  
Adrián González-López ◽  
...  
Keyword(s):  
Gene Expression ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Peripheral Blood ◽  
Blood Cells ◽  
Trinucleotide Repeat ◽  
Neurodegenerative Disorder ◽  
Gene Expression Signature ◽  
Interferon Response ◽  
Peripheral Blood Cells

Huntington's disease (HD) is an autosomal dominantly inherited neurodegenerative disorder caused by a trinucleotide repeat expansion in the Huntingtin gene. As disease-modifying therapies for HD are being developed, peripheral blood cells may be used to indicate disease progression and to monitor treatment response. In order to investigate whether gene expression changes can be found in the blood of individuals with HD that distinguish them from healthy controls, we performed transcriptome analysis by next-generation sequencing (RNA-seq). We detected a gene expression signature consistent with dysregulation of immune-related functions and inflammatory response in peripheral blood from HD cases vs. controls, including induction of the interferon response genes, IFITM3, IFI6 and IRF7. Our results suggest that it is possible to detect gene expression changes in blood samples from individuals with HD, which may reflect the immune pathology associated with the disease.

scholarly journals Esculetin Provides Neuroprotection against Mutant Huntingtin-Induced Toxicity in Huntington’s Disease Models

2021 ◽  
Vol 14 (10) ◽  
pp. 1044
Author(s):  
Letizia Pruccoli ◽  
Carlo Breda ◽  
Gabriella Teti ◽  
Mirella Falconi ◽  
Flaviano Giorgini ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Neuronal Death ◽  
Trinucleotide Repeat ◽  
Neurodegenerative Disorder ◽  
Positive Impact ◽  
Neuroprotective Effects ◽  
Drosophila Model ◽  
Exon 1 ◽  
Transgenic Drosophila

Huntington’s disease (HD) is a neurodegenerative disorder caused by an abnormal CAG trinucleotide repeat expansion within exon 1 of the huntingtin (HTT) gene. This mutation leads to the production of mutant HTT (mHTT) protein which triggers neuronal death through several mechanisms. Here, we investigated the neuroprotective effects of esculetin (ESC), a bioactive phenolic compound, in an inducible PC12 model and a transgenic Drosophila melanogaster model of HD, both of which express mHTT fragments. ESC partially inhibited the progression of mHTT aggregation and reduced neuronal death through its ability to counteract the oxidative stress and mitochondria impairment elicited by mHTT in the PC12 model. The ability of ESC to counteract neuronal death was also confirmed in the transgenic Drosophila model. Although ESC did not modify the lifespan of the transgenic Drosophila, it still seemed to have a positive impact on the HD phenotype of this model. Based on our findings, ESC may be further studied as a potential neuroprotective agent in a rodent transgenic model of HD.

scholarly journals Non-Cell Autonomous and Epigenetic Mechanisms of Huntington’s Disease

2021 ◽  
Vol 22 (22) ◽  
pp. 12499
Author(s):  
Chaebin Kim ◽  
Ali Yousefian-Jazi ◽  
Seung-Hye Choi ◽  
Inyoung Chang ◽  
Junghee Lee ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Trinucleotide Repeat ◽  
Neurodegenerative Disorder ◽  
Involuntary Movement ◽  
Therapeutic Approaches ◽  
Exon 1 ◽  
Human Chromosome 4 ◽  
The Brain

Huntington’s disease (HD) is a rare neurodegenerative disorder caused by an expansion of CAG trinucleotide repeat located in the exon 1 of Huntingtin (HTT) gene in human chromosome 4. The HTT protein is ubiquitously expressed in the brain. Specifically, mutant HTT (mHTT) protein-mediated toxicity leads to a dramatic degeneration of the striatum among many regions of the brain. HD symptoms exhibit a major involuntary movement followed by cognitive and psychiatric dysfunctions. In this review, we address the conventional role of wild type HTT (wtHTT) and how mHTT protein disrupts the function of medium spiny neurons (MSNs). We also discuss how mHTT modulates epigenetic modifications and transcriptional pathways in MSNs. In addition, we define how non-cell autonomous pathways lead to damage and death of MSNs under HD pathological conditions. Lastly, we overview therapeutic approaches for HD. Together, understanding of precise neuropathological mechanisms of HD may improve therapeutic approaches to treat the onset and progression of HD.

scholarly journals Altered cerebrovascular response to acute exercise in patients with Huntington’s disease

2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Jessica J Steventon ◽  
Hannah Furby ◽  
James Ralph ◽  
Peter O’Callaghan ◽  
Anne E Rosser ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Cerebral Perfusion ◽  
Acute Exercise ◽  
Exercise Intervention ◽  
Trinucleotide Repeat ◽  
Moderate Intensity ◽  
Activity Levels ◽  
Precentral Gyrus ◽  
Time Dynamics

Abstract The objective of this study was to determine whether a single session of exercise was sufficient to induce cerebral adaptations in individuals with Huntington’s disease and to explore the time dynamics of any acute cerebrovascular response. In this case–control study, we employed arterial-spin labelling MRI in 19 Huntington’s disease gene-positive participants (32–65 years, 13 males) and 19 controls (29–63 years, 10 males) matched for age, gender, body mass index and self-reported activity levels, to measure global and regional perfusion in response to 20 min of moderate-intensity cycling. Cerebral perfusion was measured at baseline and 15, 40 and 60 min after exercise cessation. Relative to baseline, we found that cerebral perfusion increased in patients with Huntington’s disease yet was unchanged in control participants in the precentral gyrus (P = 0.016), middle frontal gyrus (P = 0.046) and hippocampus (P = 0.048) 40 min after exercise cessation (+15 to +32.5% change in Huntington’s disease participants, −7.7 to 0.8% change in controls). The length of the disease-causing trinucleotide repeat expansion in the huntingtin gene predicted the change in the precentral gyrus (P = 0.03) and the intensity of the exercise intervention predicted hippocampal perfusion change in Huntington’s disease participants (P < 0.001). In both groups, exercise increased hippocampal blood flow 60 min after exercise cessation (P = 0.039). These findings demonstrate the utility of acute exercise as a clinically sensitive experimental paradigm to modulate the cerebrovasculature. Twenty minutes of aerobic exercise induced transient cerebrovascular adaptations in the hippocampus and cortex selectively in Huntington’s disease participants and likely represents latent neuropathology not evident at rest.

C01 Trinucleotide repeat instability in Huntington's disease

2010 ◽  
Vol 81 (Suppl 1) ◽  
pp. A16.1-A16
Author(s):  
B A Pepers ◽  
J T den Dunnen ◽  
G-J B van Ommen ◽  
W M C van Roon-Mom
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Trinucleotide Repeat ◽  
Repeat Instability

Distribution of trinucleotide repeat sequences across a 2 Mbp region containing the Huntington's disease gene

1994 ◽  
Vol 3 (1) ◽  
pp. 73-78 ◽  
Author(s):  
H. Hummerich ◽  
S. Baxendale ◽  
R. Mott ◽  
S. F.Kirby ◽  
M. E.MacDonald ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Disease Gene ◽  
Trinucleotide Repeat ◽  
Repeat Sequences

Huntington’s Disease in a Historical Context

2014 ◽  
Author(s):  
Peter S. Harper
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Positional Cloning ◽  
Ethical Issues ◽  
Trinucleotide Repeat ◽  
Historical Context ◽  
Disease Genes ◽  
Mendelian Disorders ◽  
Research Collaborations ◽  
Genetic Features

Huntington’s disease (HD) provides a paradigm for advancement of our understanding of numerous inherited brain degenerations. The classic 1872 description by George Huntington led to its recognition worldwide. HD was one of the first clearly Mendelian disorders recognized, but also one closely linked to abuses of eugenics. It has provided a model for analyzing unusual genetic features, notably genetic anticipation, and for positional cloning of disease genes. The finding that its molecular basis is an unstable trinucleotide repeat expansion coding for polyglutamine has led to an increasing understanding of its pathogenesis and possibilities for therapy. HD has been a prototype for the wise use of genetic testing and for recognition of the ethical issues that can arise, especially in presymptomatic testing. It has provided a model for international research collaborations, for development of lay associations to support patients and families, and for the close ties between these associations and research workers.

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