The scientific community has taken a huge leap towards understanding Huntington’s disease, thanks to researchers from the University of Szeged in Hungary. A study recently published in Scientific Reports has revealed new insights into this neurodegenerative disorder by employing fruit flies (Drosophila melanogaster) as a model organism. The innovative research approach consequently suggested potential therapeutic targets for the disease.
Understanding Huntington’s Disease
It’s essential first to comprehend what Huntington’s disease is. Huntington’s disease is a serious neurodegenerative condition impacting the central nervous system. It’s due to a mutation in the HTT gene resulting in a defective huntingtin (HTT) protein. Mutant HTT proteins are cleaved into toxic fragments, causing various cellular function disruptions.
The Role of the HTT Gene and Polyglutamine Tract
The HTT gene encodes the huntingtin protein, critical for nerve cell functioning. When mutations occur in the HTT gene, it results in an expanded polyglutamine tract in the Htt protein, leading to unfolding and dysfunction. An interesting aspect about Huntington’s disease is that its severity correlates with the length of this expanded polyglutamine tract.
Huntington’s is an autosomal dominant disease, meaning a person only needs to inherit one copy of the defective gene from either parent. Each child of an affected parent stands a 50% chance of inheriting the mutation.
Symptoms and Treatment of Huntington’s Disease
Early symptoms of Huntington’s disease include forgetfulness, loss of balance, and clumsiness in performing daily tasks. As time progresses, these symptoms worsen and start affecting mood and reasoning, leading to uncontrollable movements. Affected individuals find difficulty in speaking, swallowing, and walking as the disease advances. Symptoms usually manifest between ages 30 and 50.
Currently, there is no cure for Huntington’s disease. The available treatments only help in symptom management.
Highlighting the Key Findings of the Study
In the study, researchers engineered fruit flies to express the polyglutamine tract of a mutated human HTT gene in their nervous system. They used a gene called Gal4 from baker’s yeast (Saccharomyces cerevisiae), which activates gene expression when bound to a DNA sequence known as the upstream activating sequence (UAS).
In the fruit fly genome, the Gal4/UAS system successfully allowed the expression of proteins specifically in neurons. Fruit flies with the mutated HTT gene displayed neuronal degeneration, impaired climbing ability, and reduced viability and longevity, while a ‘control’ group of fruit flies with a normal range of glutamine units in the HTT protein showed little to no effect.
It was discovered that expressing a longer glutamine tract produced symptoms resembling Huntington’s disease in humans, while the shorter tract did not.
Most importantly, researchers found that overexpression of one particular gene (out of 32 investigated genes in flies) called the Yod1 gene in flies effectively eliminated disease-like effects associated with Huntington’s disease, including neurodegeneration and motor impairments. This finding could potentially be a breakthrough in the search for a cure for this debilitating disease.
