Anna C Pfalzer, Shuhei Shiino, James Silverman, Simona G Codreanu, Stacy D Sherrod, John A McLean, Daniel O Claassen
BACKGROUND: Huntington's disease (HD) is a neurodegenerative disorder caused by expanded cytosine-adenine-guanine (CAG) repeats in the Huntingtin gene, resulting in the production of mutant huntingtin proteins (mHTT). Previous research has identified urea as a key metabolite elevated in HD animal models and postmortem tissues of HD patients. However, the relationship between disease course and urea elevations, along with the molecular mechanisms responsible for these disturbances remain unknown...
March 2, 2024: Journal of Huntington's Disease
Morgane Louessard, Michel Cailleret, Margot Jarrige, Julie Bigarreau, Sophie Lenoir, Noëlle Dufour, Maria Rey, Frédéric Saudou, Nicole Deglon, Anselme L Perrier
BACKGROUND: Mutations in the Huntingtin (HTT) gene cause Huntington's disease (HD), a neurodegenerative disorder. As a scaffold protein, HTT is involved in numerous cellular functions, but its normal and pathogenic functions during human forebrain development are poorly understood. OBJECTIVE: To investigate the developmental component of HD, with a specific emphasis on understanding the functions of wild-type and mutant HTT alleles during forebrain neuron development in individuals carrying HD mutations...
February 24, 2024: Journal of Huntington's Disease
Renee R Handley, Suzanne J Reid, Zoe Burch, Jessie C Jacobsen, Tammy Gillis, Kevin Correia, Skye R Rudiger, Clive J McLaughlin, C Simon Bawden, Marcy E MacDonald, Vanessa C Wheeler, Russell G Snell
Somatic instability of the huntingtin (HTT) CAG repeat mutation modifies age-at-onset of Huntington's disease (HD). Understanding the mechanism and pathogenic consequences of instability may reveal therapeutic targets. Using small-pool PCR we analyzed CAG instability in the OVT73 sheep model which expresses a full-length human cDNA HTT transgene. Analyses of five- and ten-year old sheep revealed the transgene (CAG)69 repeat was remarkably stable in liver, striatum, and other brain tissues. As OVT73 sheep at ten years old have minimal cell death and behavioral changes, our findings support instability of the HTT expanded-CAG repeat as being required for the progression of HD...
February 18, 2024: Journal of Huntington's Disease
Marian DiFiglia, Blair R Leavitt, Douglas Macdonald, Leslie M Thompson
The field of Huntington's disease research covers many different scientific disciplines, from molecular biology all the way through to clinical practice, and as our understanding of the disease has progressed over the decades, a great deal of different terminology has accrued. The field is also renowned for its collaborative spirit and use of standardized reagents, assays, datasets, models, and clinical measures, so the use of standardized terms is especially important. We have set out to determine, through a consensus exercise involving basic and clinical scientists working in the field, the most appropriate language to use across disciplines...
2024: Journal of Huntington's Disease
Cristina Sampaio, Sandra K Kostyk, Sarah J Tabrizi, Anne E Rosser
No abstract text is available yet for this article.
2024: Journal of Huntington's Disease
Niroshan Jeyakumar, Sarah N Hilmer, Armando Teixeira-Pinto, Clement T Loy
BACKGROUND: Over one third of age of onset variation in Huntington's disease is unexplained by CAG repeat length. In Alzheimer's disease, frailty partly modulates the relationship between neuropathology and dementia. OBJECTIVE: We investigated whether a multi-domain frailty index, reflecting non-genetic factors in Huntington's disease, similarly modulates the relationship between CAG repeat length and age of onset. METHODS: We created a frailty index assessing comorbidities, substance abuse, polypharmacy, and education...
November 24, 2023: Journal of Huntington's Disease
Lis Frydenreich Hasholt
Incidence of cancer is markedly reduced in patients with the hereditary neurodegenerative polyglutamine (polyQ) diseases. We have very poor knowledge of the underlying molecular mechanisms, but the expanded polyQ sequence is assumed to play a central role, because it is common to the respective disease related proteins. The inhibition seems to take place in all kinds of cells, because the lower cancer frequency applies to nearly all types of tumors and is not related with the characteristic pathological changes in specific brain tissues...
October 27, 2023: Journal of Huntington's Disease
(no author information available yet)
No abstract text is available yet for this article.
September 29, 2023: Journal of Huntington's Disease
Jyoti Dhankhar, Anju Shrivastava, Namita Agrawal
BACKGROUND: Though primarily classified as a brain disorder, surplus studies direct Huntington's disease (HD) to be a multi-system disorder affecting various tissues and organs, thus affecting overall physiology of host. Recently, we have reported that neuronal expression of mutant huntingtin induces immune dysregulation in Drosophila and may pose chronic threat to challenged individuals. Therefore, we tested the polyphenolic compound curcumin to circumvent the impact of immune dysregulation in Drosophila model of HD...
September 28, 2023: Journal of Huntington's Disease
Elna Dickson, Claes Fryklund, Rana Soylu-Kucharz, Marie Sjögren, Karin G Stenkula, Maria Björkqvist
BACKGROUND: Metabolic alterations contribute to disease onset and prognosis of Huntington's disease (HD). Weight loss in the R6/2 mouse model of HD is a consistent feature, with onset in mid-to-late stage of disease. OBJECTIVE: In the present study, we aimed to investigate molecular and functional changes in white adipose tissue (WAT) that occur at weight loss in R6/2 mice. We further elaborated on the effect of leptin-deficiency and early obesity in R6/2 mice. METHODS: We performed analyses at 12 weeks of age; a time point that coincides with the start of weight loss in our R6/2 mouse colony...
September 12, 2023: Journal of Huntington's Disease
Sebastian D McBride, Jan Ober, Jacek Dylak, William Schneider, A Jennifer Morton
BACKGROUND: Huntington's disease (HD) is characterized by a loss of control of motor function that causes the presence of abnormal eye movements at early stages. OBJECTIVE: To determine if, compared to normal sheep, HD sheep have abnormal eye movements. METHODS: We measured eye movements in a transgenic sheep model (Ovis aries) of HD using a purpose-built, head-mounted sheep oculometer. This allows us to measure saccades in sheep without the need for either behavioral training or head fixation...
September 11, 2023: Journal of Huntington's Disease
Tiziana Petrozziello, Sommer S Huntress, Ayleen L Castillo-Torres, James P Quinn, Theresa R Connors, Corinne A Auger, Alexandra N Mills, Spencer E Kim, Sophia Liu, Farah Mahmood, Adel Boudi, Muzhou Wu, Ellen Sapp, Pia Kivisäkk, Shekar R Sunderesh, Mahmoud A Pouladi, Steven E Arnold, Bradley T Hyman, H Diana Rosas, Marian DiFiglia, Ricardo Mouro Pinto, Kimberly Kegel-Gleason, Ghazaleh Sadri-Vakili
BACKGROUND: To date, it is still controversial whether tau phosphorylation plays a role in Huntington's disease (HD), as previous studies demonstrated either no alterations or increases in phosphorylated tau (pTau) in HD postmortem brain and mouse models. OBJECTIVE: The goal of this study was to determine whether total tau and pTau levels are altered in HD. METHODS: Immunohistochemistry, cellular fractionations, and western blots were used to measure tau and pTau levels in a large cohort of HD and control postmortem prefrontal cortex (PFC)...
September 5, 2023: Journal of Huntington's Disease
Ellen Sapp, Adel Boudi, Suzanne J Reid, Bianca A Trombetta, Pia Kivisäkk, Toloo Taghian, Steven E Arnold, David Howland, Heather Gray-Edwards, Kimberly B Kegel-Gleason, Marian DiFiglia
BACKGROUND: Synaptic changes occur early in patients with Huntington's disease (HD) and in mouse models of HD. An analysis of synaptic changes in HD transgenic sheep (OVT73) is fitting since they have been shown to have some phenotypes. They also have larger brains, longer lifespan, and greater motor and cognitive capacity more aligned with humans and can provide abundant biofluids for in vivo monitoring of therapeutic interventions. OBJECTIVE: The objective of this study was to determine if there were differences between 5- and 10-year-old OVT73 and wild-type (WT) sheep in levels of synaptic proteins in brain and in neurofilament light chain (NfL) in cerebrospinal fluid (CSF) and plasma...
August 29, 2023: Journal of Huntington's Disease
Erin B D Clabough, Christia Aspili, William S Fussy, James D Ingersoll, Amy Kislyakov, Elizabeth S Li, Meng-Jiuan Su, Dustin B Wiles, Thomas E Watson, Aaron J Willy, H Thomas Vinyard, Philip J Mollica Iii, James V Taylor, Cody W Smith, Dallas A Roark, Zachary P Tabrani, Harris L Thomas, Mimi Shin, B Jill Venton, David Hayes, Conor W Sipe
BACKGROUND: Huntingtin (htt) protein is an essential regulator of nervous system function through its various neuroprotective and pro-survival functions, and loss of wild-type htt function is implicated in the etiology of Huntington's disease. While its pathological role is typically understood as a toxic gain-of-function, some neuronal phenotypes also result from htt loss. Therefore, it is important to understand possible roles for htt in other physiological circumstances. OBJECTIVE: To elucidate the role of htt in the context of ethanol exposure, we investigated how loss of htt impacts behavioral and physiological responses to ethanol in Drosophila...
August 29, 2023: Journal of Huntington's Disease
Danielle A Simmons, Nadia P Belichenko, Frank M Longo
BACKGROUND: Loss of neurotrophic support in the striatum, particularly reduced brain-derived neurotrophic factor (BDNF) levels, contributes importantly to Huntington's disease (HD) pathogenesis. Another neurotrophin (NT), NT-3, is reduced in the cortex of HD patients; however, its role in HD is unknown. BDNF and NT-3 bind with high affinity to the tropomyosin receptor-kinases (Trk) B and TrkC, respectively. Targeting TrkB/TrkC may be an effective HD therapeutic strategy, as multiple links exist between their signaling pathways and HD degenerative mechanisms...
August 24, 2023: Journal of Huntington's Disease
Emily S Fitzgerald, Julie C Stout, Yifat Glikmann-Johnston, Clare Anderson, Melinda L Jackson
BACKGROUND: In healthy people, sleep and circadian disruption are linked to cognitive deficits. People with Huntington's disease (HD), who have compromised brain function and sleep and circadian disturbances, may be even more susceptible to these cognitive effects. OBJECTIVE: To conduct a comprehensive review and synthesis of the literature in HD on the associations of cognitive dysfunction with disturbed sleep and circadian rhythms. METHODS: We searched MEDLINE via OVID, CINAHL Plus, EMBASE via OVID, and PubMed in May 2023...
August 14, 2023: Journal of Huntington's Disease
Jenny Morton
No abstract text is available yet for this article.
July 15, 2023: Journal of Huntington's Disease
Blair R Leavitt, Leslie M Thompson
No abstract text is available yet for this article.
July 15, 2023: Journal of Huntington's Disease
Carlos Estevez-Fraga, Sarah J Tabrizi, Edward J Wild
In this edition of the Huntington's Disease Clinical Trials Corner, we expand on the GENERATION HD2 (tominersen) and on the Asklepios Biopharmaceutical/BrainVectis trial with AB-1001. We also comment on the recent findings from the PROOF-HD trial, and list all currently registered and ongoing clinical trials in Huntington's disease.
July 15, 2023: Journal of Huntington's Disease
Sandra Saade-Lemus, Aleksandar Videnovic
Sleep and circadian alterations are common in patients with Huntington's disease (HD). Understanding the pathophysiology of these alterations and their association with disease progression and morbidity can guide HD management. We provide a narrative review of the clinical and basic-science studies centered on sleep and circadian function on HD. Sleep/wake disturbances among HD patients share many similarities with other neurodegenerative diseases. Overall, HD patients and animal models of the disease present with sleep changes early in the clinical course of the disease, including difficulties with sleep initiation and maintenance leading to decreased sleep efficiency, and progressive deterioration of normal sleep architecture...
July 6, 2023: Journal of Huntington's Disease
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