Huntington's Disease | 02 Jan 2024

Source: TH

Why in News?

Recently, a study by researchers from the University of Szeged in Hungary published in Scientific Reports has uncovered new insights into Huntington's disease using fruit flies (Drosophila melanogaster) as a model organism.

  • This innovative approach has provided promising revelations about disease progression and potential therapeutic targets.

What is Huntington's Disease?

  • About:
    • Huntington's disease is a severe neurodegenerative disorder affecting the central nervous system.
    • It is caused by a mutation in the HTT gene, producing a faulty huntingtin (Htt) protein.
      • Mutant Htt proteins are cleaved into toxic fragments, disrupting various cellular processes.
  • HTT Gene and Polyglutamine Tract:
    • The HTT gene codes for the huntingtin protein crucial for nerve cell functioning.
      • Mutations in the HTT gene result in an expanded polyglutamine tract in the Htt protein, leading to misfolding and dysfunction.
      • The severity of Huntington's disease correlates with the length of the expanded polyglutamine tract.
    • Huntington's disease is inherited in an autosomal dominant manner, which means that a person only needs to inherit one copy of the mutated gene from either parent to develop the condition.
      • Each child of a parent with Huntington's disease has a 50% chance of inheriting the mutation.
  • Symptoms:
    • Initial symptoms include forgetfulness, loss of balance, and clumsiness in daily tasks.
    • Symptoms worsen over time, affecting mood, and reasoning, and leading to uncontrollable movements. Patients face difficulties in speaking, swallowing, and walking as the disease advances.
    • Symptoms typically emerge between ages 30-50.
  • Treatment:
    • There is currently no cure for Huntington's disease, and available treatments only alleviate symptoms.

What are the Key Highlights of 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 the expression of genes when bound to a DNA sequence called the upstream activating sequence (UAS).
  • The Gal4/UAS system works in the fruit fly genome, allowing the expression of proteins specifically in neurons.
  • Fruit flies with the mutated HTT gene displayed neuronal degeneration, impaired climbing ability, and lower viability and longevity.
  • A 'control' group of fruit flies with a normal range of glutamine units in the HTT protein showed little to no effect.
  • The study found that expressing a longer glutamine tract produced symptoms resembling Huntington’s disease in humans, while the shorter tract did not.
  • Researchers found that overexpression of one gene (out of 32 investigated genes in flies) called Yod1 gene in flies effectively eliminated disease-like effects associated with Huntington's disease, including neurodegeneration and motor impairments.