Confirming a Drosophila Melanogaster Model of Huntingtin Aggregation

Abstract For decades, doctors, psychologists, and psychiatrists alike have struggled to treat the symptomatic effects of Huntington’s disease. Huntington’s disease is an autosomal dominant brain disease that results in the deterioration of a person’s physical and mental state. Once a person inherits the disease, they end up dying from it more often than not. At present, there are 41,000 Americans with symptomatic Huntington’s disease, and 200,000 more are currently at-risk of inheriting the disease. Given its 50/50 chance of inheritance, there seems to be no end in sight to this degenerative ailment. My research study, however, will show that with a more robust approach, finding a cure for this disease is possible. Ultimately, the aim of this project was to test an already established model in Drosophila melanogaster regarding the “huntingtin” protein responsible for Huntington’s disease. This was achieved by first demonstrating that the flies which were modified to produce huntingtin could, in fact, produce the protein. Secondly, an experimental process was created to configure a system through which the amount of protein produced by each fly could be quantified. This quantification was vital in creating a baseline that would allow for the identification of potential therapeutic treatments in the future. In short, by establishing a quantifiable model for huntingtin, this study will pave the way to new insights on huntingtin aggregation and the identification of possible treatments for Huntington’s disease in the future.

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Generic Consistency in the Reproductive Enterprise: Ethical and Legal Implications for Exclusion Testing for Huntington's Disease

Medical Law International ◽

10.1177/096853329800300303 ◽

1998 ◽

Vol 3 (2-3) ◽

pp. 135-158 ◽

Cited By ~ 2

Author(s):

Deryck Beyleveld ◽

Oliver Quarrell ◽

Stuart Toddington

Keyword(s):

At Risk ◽

Huntington's Disease ◽

Huntington’S Disease ◽

Moral Status ◽

Negative Test ◽

Legal Implications ◽

The Future ◽

Future Child ◽

Affected Parent

This paper applies Alan Gewirth's Principle of Generic Consistency (PGC) to assess the morality of exclusion testing for Huntington's Disease (HD). Part 1 presents the PGC and outlines ways in which its use may be justified. Part 2 considers how the PGC might grant protection to potential agents as such (the moral status of which is problematic under the PGC). Part 3 contends that the morality of exclusion testing rests not only on its implications for the fetus (at most a potential agent), but also on the intended relations between the possibly affected parent and the future “child-when-agent” (CA) (born after a negative test) that are intrinsic consequences of the central motivation for exclusion testing. Part 4 argues that the PGC renders it immoral, all things being equal, to permit exclusion tests on the fetus unless CA is granted (under specified circumstances) a right to find out whether the at risk parent is carrying the mutation for HD, with the implication that it is morally wrong for the at risk parent to be provided with the results of an exclusion test unless a legally binding duty is imposed on him or her to undergo a mutation test at CA's request. This right and its correlative duty might, however, be overridden by conflicting rights-considerations. The complexities of such an assessment are indicated.

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A comparison of neurological, metabolic, structural, and genetic evaluations in persons at risk for Huntington's disease

Annals of Neurology ◽

10.1002/ana.410280503 ◽

1990 ◽

Vol 28 (5) ◽

pp. 614-621 ◽

Cited By ~ 79

Author(s):

Scott T. Grafton ◽

John C. Mazziotta ◽

Jorg J. Pahl ◽

Peter St. George-Hyslop ◽

Jonathan L. Haines ◽

...

Keyword(s):

At Risk ◽

Huntington's Disease ◽

Huntington’S Disease ◽

Genetic Evaluations

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Young People Living at Risk of Huntington’s Disease: The Lived Experience

Journal of Huntington s Disease ◽

10.3233/jhd-180308 ◽

2018 ◽

Vol 7 (4) ◽

pp. 391-402 ◽

Cited By ~ 2

Author(s):

Miranda F. Lewit-Mendes ◽

Georgia C. Lowe ◽

Sharon Lewis ◽

Louise A. Corben ◽

Martin B. Delatycki

Keyword(s):

At Risk ◽

Young People ◽

Huntington's Disease ◽

Lived Experience ◽

Huntington’S Disease

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Perceptions about Research Participation among Individuals at Risk and Individuals with Premanifest Huntington’s Disease: A Survey Conducted by the European Huntington Association

Journal of Personalized Medicine ◽

10.3390/jpm11080815 ◽

2021 ◽

Vol 11 (8) ◽

pp. 815

Author(s):

Filipa Júlio ◽

Ruth Blanco ◽

Josè Perez Casanova ◽

Barbara D’Alessio ◽

Beatrice De Schepper ◽

...

Keyword(s):

At Risk ◽

Huntington's Disease ◽

Huntington’S Disease ◽

Research Participation ◽

Willingness To Participate ◽

Research Experience ◽

Research Information ◽

Research Knowledge ◽

Patient Organizations ◽

Motivation To Participate

There has been great progress in Huntington’s disease (HD) research. Yet, effective treatments to halt disease before the onset of disabling symptoms are still unavailable. Scientific breakthroughs require an active and lasting commitment from families. However, they are traditionally less involved and heard in studies. Accordingly, the European Huntington Association (EHA) surveyed individuals at risk (HDRisk) and with premanifest HD (PreHD) to determine which factors affect their willingness to participate in research. Questions assessed research experience and knowledge, information sources, reasons for involvement and noninvolvement, and factors preventing and facilitating participation. The survey included 525 individuals, of which 68.8% never participated in studies and 38.6% reported limited research knowledge. Furthermore, 52% trusted patient organizations to get research information. Reasons for involvement were altruistic and more important than reasons for noninvolvement, which were related to negative emotions. Obstacles included time/financial constraints and invasive procedures, while professional support was seen as a facilitator. PreHD individuals reported less obstacles to research participation than HDRisk individuals. Overall, a high motivation to participate in research was noted, despite limited experience and literacy. This motivation is influenced by subjective and objective factors and, importantly, by HD status. Patient organizations have a key role in fostering motivation through education and support.

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Genetic counselling: a new diagnosis in the family

Huntington's Disease ◽

10.1093/oso/9780198844389.003.0007 ◽

2020 ◽

pp. 64-71

Author(s):

Oliver Quarrell

Keyword(s):

At Risk ◽

Huntington's Disease ◽

Huntington’S Disease ◽

Genetic Counselling ◽

Genetic Disorders ◽

Medical Doctors ◽

Genetic Tests ◽

The Family ◽

Close Relatives ◽

New Diagnosis

This chapter describes the process of genetic counselling in general but with an emphasis on Huntington’s disease. The chapter discusses issues for a new diagnosis in the family and describes the challenges of telling children that they are at risk. Medical doctors often lead genetic counselling teams as they are specially trained to give information about genetic disorders and explain the implications of genetic tests. The doctor or counsellor has to understand your particular circumstances and support you in a way that allows you to make your own decisions. A diagnosis of HD has implications for you and all your close relatives.

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Huntington’s Disease—An Outlook on the Interplay of the HTT Protein, Microtubules and Actin Cytoskeletal Components

Cells ◽

10.3390/cells9061514 ◽

2020 ◽

Vol 9 (6) ◽

pp. 1514 ◽

Cited By ~ 2

Author(s):

Aleksandra S. Taran ◽

Lilia D. Shuvalova ◽

Maria A. Lagarkova ◽

Irina B. Alieva

Keyword(s):

Huntington's Disease ◽

Huntington’S Disease ◽

Autosomal Dominant ◽

Cell Physiology ◽

Mutant Form ◽

Striatal Neurons ◽

Molecular Processes ◽

Wild Type ◽

Cellular Processes ◽

Cell Structures

Huntington’s disease is a severe and currently incurable neurodegenerative disease. An autosomal dominant mutation in the Huntingtin gene (HTT) causes an increase in the polyglutamine fragment length at the protein N-terminus. The consequence of the mutation is the death of neurons, mostly striatal neurons, leading to the occurrence of a complex of motor, cognitive and emotional-volitional personality sphere disorders in carriers. Despite intensive studies, the functions of both mutant and wild-type huntingtin remain poorly understood. Surprisingly, there is the selective effect of the mutant form of HTT even on nervous tissue, whereas the protein is expressed ubiquitously. Huntingtin plays a role in cell physiology and affects cell transport, endocytosis, protein degradation and other cellular and molecular processes. Our experimental data mining let us conclude that a significant part of the Huntingtin-involved cellular processes is mediated by microtubules and other cytoskeletal cell structures. The review attempts to look at unresolved issues in the study of the huntingtin and its mutant form, including their functions affecting microtubules and other components of the cell cytoskeleton.

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Huntington's disease: prediction and prevention

Philosophical Transactions of the Royal Society of London Series B Biological Sciences ◽

10.1098/rstb.1988.0050 ◽

1988 ◽

Vol 319 (1194) ◽

pp. 285-298 ◽

Cited By ~ 7

Keyword(s):

At Risk ◽

Huntington's Disease ◽

Huntington’S Disease ◽

Late Onset ◽

Predictive Test ◽

Prediction And Prevention ◽

Feasible Alternative ◽

Dna Restriction ◽

The Individual ◽

First Time

The identification of a DNA restriction fragment length polymorphism closely linked to Huntington’s disease on the short arm of chromosome 4 has for the first time allowed presymptomatic prediction to be undertaken in first-degree relatives at risk. The late and variable onset of this dominantly inherited disorder makes such prediction a powerful and potentially valuable aid in genetic counselling, but in the absence of effective therapy there are serious ethical reservations concerning such a predictive test. The new developments have stimulated an active and informative debate among professionals and family members on whether and how predictive tests should be used. Guidelines have emerged which should be useful not only for Huntington’s disease, but for other serious late-onset neurogenetic disorders. Meanwhile, studies in Wales and elsewhere have not only confirmed the original linkage but have excluded multi-locus heterogeneity as a significant problem. Genetic prediction for the individual at risk remains critically dependent on a suitable family structure, present in only a minority of families in Wales. A more feasible alternative for most families is prenatal exclusion, which can allow risk prediction for a pregnancy without altering the situation for the person at risk. This approach has already been applied in Wales; the experience gained will be useful in full prediction, which is currently being introduced.

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