Ways to Help Break Down Mutant Huntingtin Protein and Potential Treatments

Huntington's Disease is linked to the formation of toxic mutant HTT fragments due to a CAG-repeat expansion in the HTT gene.

• Mutant HTT fragments with expanded polyglutamine are toxic and prone to aggregation, especially affecting striatal neurons.
• The absence of disease-modifying treatments for Huntington's Disease highlights the need for new therapeutic strategies.
• Reducing the levels of toxic mHTT fragments may prevent their aggregation and delay disease onset.
• The ubiquitin-proteasome system is functional in Huntington's Disease, suggesting potential for targeted degradation strategies.
• Three strategies for modulating mHTT levels include targeting ubiquitin-modifying enzymes, using engineered small molecules for selective degradation, and employing HTT-specific intracellular antibodies for gene therapy.

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