Huntington's disease: delayed hypersensitivity in vitro to human central nervous system antigens

Science ◽  
1977 ◽  
Vol 195 (4275) ◽  
pp. 314-316 ◽  
Author(s):  
D. Barkley ◽  
S Hardiwidjaja ◽  
J. Menkes
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Delayed Hypersensitivity ◽  
Human Central Nervous System

scholarly journals Emerging Roles of Exosomes in Huntington’s Disease

2021 ◽  
Vol 22 (8) ◽  
pp. 4085
Author(s):  
Hanadi Ananbeh ◽  
Petr Vodicka ◽  
Helena Kupcova Skalnikova
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Neurodegenerative Disorder ◽  
Cell Types ◽  
Neuroprotective Effects ◽  
The Central Nervous System

Huntington’s disease (HD) is a rare hereditary autosomal dominant neurodegenerative disorder, which is caused by expression of mutant huntingtin protein (mHTT) with an abnormal number of glutamine repeats in its N terminus, and characterized by intracellular mHTT aggregates (inclusions) in the brain. Exosomes are small extracellular vesicles that are secreted generally by all cell types and can be isolated from almost all body fluids such as blood, urine, saliva, and cerebrospinal fluid. Exosomes may participate in the spreading of toxic misfolded proteins across the central nervous system in neurodegenerative diseases. In HD, such propagation of mHTT was observed both in vitro and in vivo. On the other hand, exosomes might carry molecules with neuroprotective effects. In addition, due to their capability to cross blood-brain barrier, exosomes hold great potential as sources of biomarkers available from periphery or carriers of therapeutics into the central nervous system. In this review, we discuss the emerging roles of exosomes in HD pathogenesis, diagnosis, and therapy.

scholarly journals Huntington's Disease: Two-Year Observational Follow-Up of Executive Function Evaluation with CNS Vital Signs Test in an Adult Patient

2011 ◽  
Vol 2011 ◽  
pp. 1-4
Author(s):  
Anna Lucia Spear King ◽  
Alexandre Martins Valença ◽  
Adriana Cardoso de Oliveira e Silva ◽  
Ana Claudia Cerqueira ◽  
Lígia Maria Chaves Ferraz ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Vital Signs ◽  
Clinical Severity ◽  
Psychomotor Development ◽  
Cognitive State ◽  
Evolutionary Stage ◽  
Medication Therapy

Huntington's disease (HD) is a genetic, degenerative, and progressive central nervous system disease. It is characterized by motor abnormalities and cognitive and psychiatric symptoms.Objective. To describe the precise degree of clinical severity of patients with HD through a new neurocognitive assessment.Methods. Unprecedented battery of computerized tests, CNSVS (Central Nervous System Vital Signs), was applied at three different moments in 2008, 2009, and 2010. The accurate and reliable CNSVS objectively provided the cognitive state of patients and allowed for the evaluation of disease progression.Case Report. P., 26, female, without any medication, with normal psychomotor development is a parent carrier of HD. In 2008, she was diagnosed with HD in accordance with the Medical Genetics Laboratories.Conclusion. The tests may be useful to reveal the exact measure of the current evolutionary stage of HD patients, allowing for more efficient planning of treatment and future procedures, such as the medication, therapy, and physical activity to be administered.

scholarly journals Synthetic lethal screening in the mammalian central nervous system identifies Gpx6 as a modulator of Huntington’s disease

2014 ◽  
Vol 112 (1) ◽  
pp. 268-272 ◽  
Author(s):  
Reut Shema ◽  
Ruth Kulicke ◽  
Glenn S. Cowley ◽  
Rachael Stein ◽  
David E. Root ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Mouse Model ◽  
Neurodegenerative Disease ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Model Organisms ◽  
Mutant Huntingtin ◽  
Synthetic Lethal ◽  
Mammalian Central Nervous System

Huntington’s disease, the most common inherited neurodegenerative disease, is characterized by a dramatic loss of deep-layer cortical and striatal neurons, as well as morbidity in midlife. Human genetic studies led to the identification of the causative gene, huntingtin. Recent genomic advances have also led to the identification of hundreds of potential interacting partners for huntingtin protein and many hypotheses as to the molecular mechanisms whereby mutant huntingtin leads to cellular dysfunction and death. However, the multitude of possible interacting partners and cellular pathways affected by mutant huntingtin has complicated efforts to understand the etiology of this disease, and to date no curative therapeutic exists. To address the general problem of identifying the disease-phenotype contributing genes from a large number of correlative studies, here we develop a synthetic lethal screening methodology for the mammalian central nervous system, called SLIC, for synthetic lethal in the central nervous system. Applying SLIC to the study of Huntington’s disease, we identify the age-regulated glutathione peroxidase 6 (Gpx6) gene as a modulator of mutant huntingtin toxicity and show that overexpression of Gpx6 can dramatically alleviate both behavioral and molecular phenotypes associated with a mouse model of Huntington’s disease. SLIC can, in principle, be used in the study of any neurodegenerative disease for which a mouse model exists, promising to reveal modulators of neurodegenerative disease in an unbiased fashion, akin to screens in simpler model organisms.

scholarly journals Towards human central nervous system in vitro models for preclinical research: strategies for 3D neural cell culture

2011 ◽  
Vol 5 (Suppl 8) ◽  
pp. P53 ◽  
Author(s):  
Daniel Simão ◽  
Inês Costa ◽  
Margarida Serra ◽  
Johannes Schwarz ◽  
Catarina Brito ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Cell Culture ◽  
Nervous System ◽  
In Vitro Models ◽  
Neural Cell ◽  
Research Strategies ◽  
Human Central Nervous System ◽  
Preclinical Research

scholarly journals Peripheral Htt silencing does not ameliorate central signs of disease in the B6. HttQ111/+ mouse model of Huntington’s Disease

2016 ◽  
Author(s):  
Sydney R. Coffey ◽  
Robert M. Bragg ◽  
Minnig Shawn ◽  
Seth A. Ament ◽  
Glickenhaus Anne ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Transcriptional Dysregulation ◽  
Time Period ◽  
Organ Systems ◽  
Wide Range ◽  
The Central Nervous System ◽  
The Relationship

AbstractHuntington’s disease (HD) is an autosomal dominant neurodegenerative disease whose neuropathological signature is a selective loss of medium spiny neurons in the striatum. Despite this selective neuropathology, the mutant protein (huntingtin) is found in virtually every cell so far studied, and, consequently, phenotypes are observed in a wide range of organ systems both inside and outside the central nervous system. We, and others, have suggested that peripheral dysfunction could contribute to the rate of progression of striatal phenotypes of HD. To test this hypothesis, we lowered levels of huntingtin by treating mice with antisense oligonucleotides (ASOs) targeting the murine Huntingtin gene. To study the relationship between peripheral huntingtin levels and striatal HD phenotypes, we utilized a knock-in model of the human HD mutation (the B6.HttQ111/+ mouse). We treated mice with ASOs from 2-10 months of age, a time period over which significant HD-relevant signs progressively develop in the brains of HttQ111+ mice. Peripheral treatment with ASOs led to persistent reduction of huntingtin protein in peripheral organs, including liver, brown and white adipose tissues. This reduction was not associated with alterations in the severity of HD-relevant signs in the striatum of HttQ111/+ mice at the end of the study, including transcriptional dysregulation, the accumulation of neuronal intranuclear inclusions, and behavioral changes such as subtle hypoactivity and reduced exploratory drive. These results suggest that the amount of peripheral reduction achieved in the current study does not significantly impact the progression of HD-relevant signs in the central nervous system.

Dispersion of central nervous system tumors

1974 ◽  
Vol 41 (6) ◽  
pp. 691-698 ◽  
Author(s):  
Ulrich Batzdorf ◽  
Vivian Gold
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Central Nervous System Tumors ◽  
Tissue Cultures ◽  
Human Central Nervous System ◽  
Content Type ◽  
Nervous System Tumors ◽  
Mechanical Factors ◽  
Made In

✓ The phenomenon of tumor dispersion through cerebrospinal fluid is discussed in relation to observations made in tissue cultures of human central nervous system tumors. Satellite colony formation was observed in cultures of tumors that tend to spread through the CSF. Abnormalities of the tumor cell surface, particularly a reduction of cell-to-cell adhesiveness, probably are important. Although mechanical factors contribute to the formation of both CSF metastases and in vitro satellites, they do not offer a sufficient explanation for these phenomena.

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