Mutant huntingtin protein

Definition

Mutant huntingtin protein is an altered form of the huntingtin protein that arises from a genetic mutation in the HTT gene, which is associated with Huntington's disease. This abnormal protein leads to neurodegeneration, particularly in areas of the brain responsible for movement and cognition, contributing to the symptoms seen in neurodegenerative disorders.

5 Must Know Facts For Your Next Test

1. Mutant huntingtin protein is characterized by an expanded polyglutamine (polyQ) tract, resulting from the CAG repeat expansion in the HTT gene.
2. The presence of mutant huntingtin protein triggers a cascade of cellular dysfunctions, including mitochondrial impairment and excitotoxicity, leading to neuronal death.
3. Huntington's disease typically manifests in mid-adulthood, with symptoms such as chorea, cognitive decline, and psychiatric issues being linked to the toxicity of mutant huntingtin protein.
4. Research is ongoing to develop therapies that target mutant huntingtin protein, including gene silencing techniques that aim to reduce its production in affected individuals.
5. Animal models have been instrumental in studying the effects of mutant huntingtin protein, helping to elucidate mechanisms of disease progression and potential therapeutic approaches.

Review Questions

• How does the structure of mutant huntingtin protein differ from normal huntingtin protein, and what implications does this have for neuronal function?
  • Mutant huntingtin protein differs from normal huntingtin due to an expanded polyglutamine tract resulting from CAG repeat expansion. This structural change makes the mutant form more prone to misfolding and aggregation, disrupting normal cellular functions and leading to neurotoxicity. The aggregates can interfere with various cellular processes like gene expression and protein degradation, ultimately resulting in neuronal dysfunction and cell death.
• Discuss the role of mutant huntingtin protein in the pathophysiology of Huntington's disease and its effects on brain regions.
  • Mutant huntingtin protein plays a central role in the pathophysiology of Huntington's disease by promoting neurodegeneration, especially in the striatum and cortex. The accumulation of this toxic protein disrupts synaptic signaling and leads to neuronal loss, contributing to the hallmark symptoms of motor dysfunction, cognitive decline, and behavioral changes. This neurodegeneration results in progressive disability for affected individuals and highlights the critical importance of targeting mutant huntingtin for potential treatments.
• Evaluate current research strategies aimed at addressing the impact of mutant huntingtin protein on neurodegeneration and their potential clinical applications.
  • Current research strategies include gene silencing approaches like antisense oligonucleotides that specifically target the mRNA encoding mutant huntingtin protein, thereby reducing its production. Other methods involve small molecules that prevent aggregation or promote clearance of mutant forms. These strategies are being evaluated in clinical trials, with hopes that they will slow disease progression and improve quality of life for those affected by Huntington's disease. As understanding deepens around mutant huntingtin's role in neurodegeneration, these innovative therapies could significantly alter treatment paradigms.

Related terms

Huntington's disease: A hereditary neurodegenerative disorder caused by the expansion of CAG repeats in the HTT gene, leading to the production of mutant huntingtin protein.

Neurodegeneration: The progressive loss of structure or function of neurons, which can be caused by factors such as toxic proteins, inflammation, and oxidative stress.

CAG repeat expansion: The genetic alteration characterized by the abnormal repetition of the CAG sequence in the HTT gene, responsible for producing the toxic mutant huntingtin protein.