scholarly journals The Role of Pretraining on Skilled Forelimb Use in an Animal Model of Huntington's Disease

2003 ◽  
Vol 12 (3) ◽  
pp. 257-264 ◽  
Author(s):  
R. A. Fricker-Gates ◽  
R. Smith ◽  
J. Muhith ◽  
S. B. Dunnett
Keyword(s):  
Animal Model ◽  
Huntington's Disease ◽  
Huntington’S Disease

Curcumin dietary supplementation ameliorates disease phenotype in an animal model of Huntington’s disease.

2019 ◽  
Author(s):  
F Elifani ◽  
E Amico ◽  
G Pepe ◽  
L Capocci ◽  
S Castaldo ◽  
...  
Keyword(s):  
Animal Model ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Body Weight Loss ◽  
Beneficial Effects ◽  
Naturally Occurring ◽  
Human Pathology ◽  
The Brain

Abstract Huntington’s disease (HD) has traditionally been described as a disorder purely of the brain, however evidence indicates that peripheral abnormalities are also commonly seen. Among others, severe unintended body weight loss represents a prevalent and often debilitating feature of HD pathology, with no therapies available. It correlates with disease progression and significantly affects the quality of life of HD patients. Curcumin, a naturally occurring polyphenol with multiple therapeutic properties, has been validated to exert important beneficial effects under health conditions as well as in different pathological settings, including neurodegenerative and gastrointestinal (GI) disorders. Here, we investigated the potential therapeutic action that curcumin-supplemented diet may exert on central and peripheral dysfunctions in R6/2 mice, a well-characterized HD animal model which recapitulates some features of human pathology. Maintenance of normal motor function, protection from neuropathology and from GI dysfunction, preservation of GI emptying, and conserved intestinal contractility, proved the beneficial role of life-long dietary curcumin in HD and corroborated the potential of the compound to be exploited to alleviate very debilitating symptoms associated with the disease.

The Role of Melatonin in Multiple Sclerosis, Huntington's Disease and Cerebral Ischemia

2014 ◽  
Vol 13 (6) ◽  
pp. 1096-1119 ◽  
Author(s):  
Begona Escribano ◽  
Ana Colin-Gonzalez ◽  
Abel Santamaria ◽  
Isaac Tunez
Keyword(s):  
Multiple Sclerosis ◽  
Cerebral Ischemia ◽  
Huntington's Disease ◽  
Huntington’S Disease

scholarly journals A modular tool to query and inducibly disrupt biomolecular condensates

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Carmen N. Hernández-Candia ◽  
Sarah Pearce ◽  
Chandra L. Tucker
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Cellular Function ◽  
Biological Role ◽  
Cellular Biology ◽  
Condensate Formation ◽  
Health And Disease ◽  
Lateral Sclerosis

AbstractDynamic membraneless compartments formed by protein condensates have multifunctional roles in cellular biology. Tools that inducibly trigger condensate formation have been useful for exploring their cellular function, however, there are few tools that provide inducible control over condensate disruption. To address this need we developed DisCo (Disassembly of Condensates), which relies on the use of chemical dimerizers to inducibly recruit a ligand to the condensate-forming protein, triggering condensate dissociation. We demonstrate use of DisCo to disrupt condensates of FUS, associated with amyotrophic lateral sclerosis, and to prevent formation of polyglutamine-containing huntingtin condensates, associated with Huntington’s disease. In addition, we combined DisCo with a tool to induce condensates with light, CRY2olig, achieving bidirectional control of condensate formation and disassembly using orthogonal inputs of light and rapamycin. Our results demonstrate a method to manipulate condensate states that will have broad utility, enabling better understanding of the biological role of condensates in health and disease.

Huntington's disease and its animal model: Alterations in kainic acid binding

Life Sciences ◽  
1979 ◽  
Vol 24 (9) ◽  
pp. 809-816 ◽  
Author(s):  
Kevin Beaumont ◽  
Yves Maurin ◽  
Terry D. Reisine ◽  
Jeremy Z. Fields ◽  
Ernest Spokes ◽  
...  
Keyword(s):  
Animal Model ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Kainic Acid

Huntingtin Polyglutamine Fragments Are a Substrate for Hsp104 in Yeast

2021 ◽  
Author(s):  
Nicole J. Wayne ◽  
Katherine E. Dembny ◽  
Tyler Pease ◽  
Farrin Saba ◽  
Xiaohong Zhao ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Essential Role ◽  
Marked Effect ◽  
Yeast Prion ◽  
Rich Region ◽  
Polyglutamine Repeat ◽  
Prion Propagation

The aggregation of huntingtin fragments with expanded polyglutamine repeat regions (HttpolyQ) that cause Huntington’s disease depends on the presence of a prion with an amyloid conformation in yeast. As a result of this relationship, HttpolyQ aggregation indirectly depends on Hsp104 due to its essential role in prion propagation. We find that HttQ103 aggregation is directly affected by Hsp104 with and without the presence of [ RNQ + ] and [ PSI + ] prions. When we inactivate Hsp104 in the presence of prion, yeast have only one or a few large HttQ103 aggregates rather than numerous smaller aggregates. When we inactivate Hsp104 in the absence of prion, there is no significant aggregation of HttQ103; whereas with active Hsp104, HttQ103 aggregates slowly accumulate due to the severing of spontaneously nucleated aggregates by Hsp104. We do not observe either effect with HttQ103P, which has a polyproline-rich region downstream of the polyglutamine region, because HttQ103P does not spontaneously nucleate and Hsp104 does not efficiently sever the prion-nucleated HttQ103P aggregates. Therefore, the only role of Hsp104 in HttQ103P aggregation is to propagate yeast prion. In conclusion, because Hsp104 efficiently severs the HttQ103 aggregates, but not HttQ103P aggregates, it has a marked effect on the aggregation of HttQ103, but not HttQ103P.

Excitotoxic brain damage involves early peroxynitrite formation in a model of Huntington’s disease in rats: Protective role of iron porphyrinate 5,10,15,20-tetrakis (4-sulfonatophenyl)porphyrinate iron (III)

Neuroscience ◽  
2005 ◽  
Vol 135 (2) ◽  
pp. 463-474 ◽  
Author(s):  
V. Pérez-De La Cruz ◽  
C. González-Cortés ◽  
S. Galván-Arzate ◽  
O.N. Medina-Campos ◽  
F. Pérez-Severiano ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Brain Damage ◽  
Protective Role

scholarly journals Striatal Chloride Dysregulation and Impaired GABAergic Signaling Due to Cation-Chloride Cotransporter Dysfunction in Huntington’s Disease

2022 ◽  
Vol 15 ◽  
Author(s):  
Melissa Serranilla ◽  
Melanie A. Woodin
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Neurological Disorders ◽  
Synaptic Inhibition ◽  
Motor Impairments ◽  
Immature Brain ◽  
Amino Butyric Acid ◽  
Mature Neurons ◽  
Cation Chloride Cotransporters

Intracellular chloride (Cl–) levels in mature neurons must be tightly regulated for the maintenance of fast synaptic inhibition. In the mature central nervous system (CNS), synaptic inhibition is primarily mediated by gamma-amino butyric acid (GABA), which binds to Cl– permeable GABAA receptors (GABAARs). The intracellular Cl– concentration is primarily maintained by the antagonistic actions of two cation-chloride cotransporters (CCCs): Cl–-importing Na+-K+-Cl– co-transporter-1 (NKCC1) and Cl– -exporting K+-Cl– co-transporter-2 (KCC2). In mature neurons in the healthy brain, KCC2 expression is higher than NKCC1, leading to lower levels of intracellular Cl–, and Cl– influx upon GABAAR activation. However, in neurons of the immature brain or in neurological disorders such as epilepsy and traumatic brain injury, impaired KCC2 function and/or enhanced NKCC1 expression lead to intracellular Cl– accumulation and GABA-mediated excitation. In Huntington’s disease (HD), KCC2- and NKCC1-mediated Cl–-regulation are also altered, which leads to GABA-mediated excitation and contributes to the development of cognitive and motor impairments. This review summarizes the role of Cl– (dys)regulation in the healthy and HD brain, with a focus on the basal ganglia (BG) circuitry and CCCs as potential therapeutic targets in the treatment 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.

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