Huntington's disease is a neurodegenerative disorder accompanied by loss of muscle coordination, cognitive decline, and mental problems. An international research team, including Korean researchers, newly revealed that the disease's causative protein, "huntingtin," is not only modified but also plays an important role in maintaining the cell cytoskeleton.
A team led by Song Ji-jun, a professor in the Department of Biological Sciences at the Korea Advanced Institute of Science and Technology (KAIST), said on the 1st that it had identified the role of the huntingtin protein in collaboration with the Institute of Science and Technology Austria (ISTA), Sorbonne University and Paris Brain Institute in France, and the Swiss Federal Institute of Technology Lausanne (EPFL). The results were published in the international journal Science Advances on Sept. 19.
Until now, huntingtin was known only to use the cytoskeleton, such as by being involved in vesicle transport or microtubule-based trafficking. The researchers studied the role of huntingtin using cryo-electron microscopy and cell biology techniques.
As a result, they discovered that huntingtin physically organizes the cytoskeleton itself. This is the world's first case proving the new role of huntingtin at the molecular level.
Huntingtin binds directly to cytoskeletal microfilaments, and a pair of huntingtin molecules aligned and bundled the cytoskeleton at intervals of about 20 nm (nanometers, one billionth of a meter). The cytoskeletal bundles formed this way played a key role in the development of neural network connections between neurons. In fact, in neurons lacking huntingtin, researchers observed impaired structural development of the neurons.
Song Ji-jun said, "This achievement not only provides an important clue to understanding the mechanism of Huntington's disease onset, but is also expected to have a large ripple effect on research into cytoskeleton-related diseases," adding, "It opens the door to newly shedding light on the role of huntingtin in various life phenomena such as cell division, migration, and mechanotransduction."
References
Science Advances (2025), DOI: https://doi.org/10.1126/sciadv.adw4124