Huntington’s disease (HD) is an inherited disorder in which the nerve cells in parts of the brain gradually break down and die. It is caused by a protein called huntingtin, which forms unnatural clumps as a result of a mutation.
However, until now it was unknown what these clumps exactly look like, unlike in other diseases caused by clumping of defective proteins, such as Alzheimer’s or Parkinson’s. An international team of scientists, including University of Groningen Professor of Solid State NMR Spectroscopy Patrick van der Wel, has used a combination of computer and experiment-based techniques to present the first detailed picture of these disease-related clumps. The study provides new insights into the ‘fuzzy coat’ that these clumps have on their surface.
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: Mahdi Bagherpoor Helabad, Irina Matlahov, Raj Kumar, Jan O. Daldrop, Greeshma Jain, Markus Weingarth, Patrick C. A. van der Wel & Markus S. Miettinen: Integrative determination of atomic structure of mutant huntingtin exon 1 fibrils implicated in Huntington disease. Nature Communications, 30 December 2024
Nature Communications
Experimental study
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Integrative determination of atomic structure of mutant huntingtin exon 1 fibrils implicated in Huntington disease
30-Dec-2024
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