Markus Miettinen, University of Bergen, Norway
Researchers mapped the unique structure of protein clumps in Huntington’s disease, opening doors to better diagnostics and treatments.
Huntington’s disease (HD) is a genetic disorder in which nerve cells in specific regions of the brain progressively deteriorate and die. The disease is caused by a mutated form of the huntingtin protein, which leads to the formation of abnormal clumps.
Unlike other protein-clumping diseases such as Alzheimer’s or Parkinson’s, the exact structure of these huntingtin clumps had remained unknown—until now.
An international team of scientists, including Professor Patrick van der Wel from the University of Groningen, has combined computational modeling with experimental techniques to reveal the first detailed image of these disease-related clumps. Their research uncovers new insights into the distinctive “fuzzy coat” that covers the surface of these protein aggregates.
Diagnostics and treatments
Similar to the clumps in Alzheimer’s and Parkinson’s, the clumps in Huntington’s disease are elongated shapes called fibrils. However, the Huntington’s fibrils differ in important ways from those in other fibril-induced diseases.
‘Knowing the structure of the protein clump is a critical piece of the puzzle of how these proteins play their role in the disease,’ says Van der Wel. It also paves the way for developing diagnostics and perhaps even treatments. ‘It’s important to monitor the disease proteins in patients, for example during experimental treatments.’ The project was supported by Huntington’s disease foundations, which are largely funded by families of patients and the general public.
Reference: “Integrative determination of atomic structure of mutant huntingtin exon 1 fibrils implicated in Huntington disease” by Mahdi Bagherpoor Helabad, Irina Matlahov, Raj Kumar, Jan O. Daldrop, Greeshma Jain, Markus Weingarth, Patrick C. A. van der Wel and Markus S. Miettinen, 30 December 2024, Nature Communications.
DOI: 10.1038/s41467-024-55062-8
