Huntington's Disease Research - Genetics, Causes, Symptoms, Treatment

Huntington's Disease Research Today is a free monthly online journal that collates and summarizes the latest research about Huntington's Disease, including details on genetics, causes, symptoms, treatment.


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A novel human embryonic stem cell-derived Huntington's disease neuronal model exhibits mutant huntingtin (mHTT) aggregates and soluble mHTT-dependent neurodegeneration.

Lu B, Palacino J

School of Life Sciences, Fudan University, Shanghai, China. luboxun@fudan.edu.cn

Most neurodegenerative diseases are linked to aberrant accumulation of aggregation-prone proteins. Among them, Huntington's disease (HD) is caused by an expanded polyglutamine repeat stretch in the N terminus of the mutant huntingtin protein (mHTT), which gets cleaved and aggregates in the brain. Recently established human induced pluripotent stem cell-derived HD neurons exhibit some disease-relevant phenotypes and provide tools for HD research. However, they have limitations such as genetic heterogeneity and an absence of mHTT aggregates and lack a robust neurodegeneration phenotype. In addition, the relationship between the phenotype and mHTT levels has not been elucidated. Herein, we present a human embryonic stem cell (hESC)-derived HD neuronal model expressing HTTexon1 fragments, which addresses the deficiencies enumerated above. The wild-type and HD lines are derived from an isogenic background and exhibit insoluble mHTT aggregates and neurodegeneration. We also demonstrate a quantitative relationship between neurodegeneration and soluble monomeric (but not oligomeric or aggregated) mHTT levels. Reduction of ~10% of mHTT is sufficient to prevent toxicity, whereas ~90% reduction of wild-type HTT is safe and well-tolerated in these cells. A known HD toxicity modifier (Rhes) showed expected rescue of neurodegeneration. Therefore, the hESC-derived neuronal models complement existing induced pluripotent stem cell-derived neuronal models and provide valuable tools for HD research.

Published 1 May 2013 in FASEB J, 27(5): 1820-9.
Full-text of this article is available online (may require subscription).


Articles on Huntington's Disease published 25 April 2013:

Multiple sources of striatal inhibition are differentially affected in Huntington's disease mouse models.   J Neurosci, 33(17): 7393-406.

In Huntington's disease (HD) mouse models, spontaneous inhibitory synaptic activity is enhanced in a subpopulation of medium-sized spiny neurons (MSNs), which could dampen striatal output. We examined the potential source(s) of increased inhibition using electrophysiological and optogenetic methods to assess feedback and feedforward inhibition in two transgenic mouse models of HD. Single whole-cell patch-clamp recordings demonstrated that increased GABA synaptic activity impinges principally on ... [Abstract] [Full-text]


Articles on Huntington's Disease published 22 April 2013:

Neuroprotective effects of PPAR-γ agonist rosiglitazone in N171-82Q mouse model of Huntington's disease.   J Neurochem, 125(3): 410-9.

Huntington's disease (HD) is a devastating genetic neurodegenerative disease caused by CAG trinucleotide expansion in the exon-1 region of the huntingtin gene. Currently, no cure is available. It is becoming increasingly apparent that mutant Huntingtin (HTT) impairs metabolic homeostasis and causes transcriptional dysregulation. The peroxisome proliferator-activated receptor gamma (PPAR-γ) is a transcriptional factor that plays a key role in regulating genes involved in energy metabolism; ... [Abstract] [Full-text]


Articles on Huntington's Disease published 11 April 2013:

Mutant Huntingtin alters retrograde transport of TrkB receptors in striatal dendrites.   J Neurosci, 33(15): 6298-309.

Huntingtin (HTT), the protein mutated in Huntington's disease (HD), controls transport of the neurotrophin, brain-derived neurotrophic factor (BDNF), within corticostriatal neurons. Transport and delivery of BDNF to the striatum are reduced in disease, which contributes to striatal neuron degeneration. BDNF released by cortical neurons activates TrkB receptors at striatal dendrites to promote striatum survival. However, it remains to be determined whether transport of TrkB, the BDNF receptor, ... [Abstract] [Full-text]


Articles on Huntington's Disease published 5 April 2013:

Enhancement of brain-type creatine kinase activity ameliorates neuronal deficits in Huntington's disease.   Biochim Biophys Acta, 1832(6): 742-53.

Huntington's disease (HD) is a hereditary neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin (HTT) gene. Brain-type creatine kinase (CKB) is an enzyme involved in energy homeostasis via the phosphocreatine-creatine kinase system. Although downregulation of CKB was previously reported in brains of HD mouse models and patients, such regulation and its functional consequence in HD are not fully understood. In the present study, we demonstrated that levels of CKB found in ... [Abstract] [Full-text]


Articles on Huntington's Disease published 25 March 2013:

Circadian and sleep disorder in Huntington's disease.   Exp Neurol, 243: 34-44.

Huntington's disease is a progressive neurological disorder that starts insidiously with motor, cognitive or psychiatric disturbance, and progresses through a distressing range of symptoms to end with a devastating loss of function, both motor and executive. There is a growing awareness that, in addition to cognitive and psychiatric symptoms, there are other important non-motor symptoms in HD, including sleep and circadian abnormalities. It is not clear if sleep-wake changes are caused directly ... [Abstract] [Full-text]


Articles on Huntington's Disease published 19 March 2013:

One-year safety and tolerability profile of pridopidine in patients with Huntington disease.   Neurology, 80(12): 1086-94.

[Abstract] [Full-text]


Articles on Huntington's Disease published 12 March 2013:

The challenge of juvenile Huntington disease: to test or not to test.   Neurology, 80(11): 990-6.

[Abstract] [Full-text]

Family history in juvenile Huntington disease: do the signs point to "yes" or "very doubtful"?   Neurology, 80(11): 976-7.

Juvenile Huntington disease (JHD)-Huntington disease (HD) with an onset ≤20 years-accounts for approximately 10% of all HD cases. Like the adult form of the disorder, JHD is a hereditary neurodegenerative disease characterized by dementia and behavioral changes, caused by an expanded CAG repeat within the first exon of the huntingtin (HTT) gene on chromosome 4.(1) Unlike the adult form, JHD tends to present with a rigid-dystonic picture or nonspecific motor and neuropsychological signs rather ... [Abstract] [Full-text]


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Huntington's Disease Research Today Archive:

Volume 1 (2005)
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Volume 2 (2006)
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Volume 3 (2007)
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Volume 4 (2008)
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Volume 5 (2009)
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Volume 6 (2010)
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Volume 7 (2011)
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Volume 8 (2012)
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Volume 9 (2013)
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Huntington's Disease Books

Juvenile Huntington's Disease: and other trinucleotide repeat disorders

Juvenile Huntington's Disease: and other trinucleotide repeat disorders