The role of mutant CYLD in frontotemporal dementia and motor neuron disease

  • Blair, Ian (Primary Chief Investigator)
  • Dobson-Stone, Carol (Chief Investigator)
  • Kwok, John B. (Chief Investigator)
  • Atkin, Julie (Chief Investigator)
  • Ooi, Lezanne (Chief Investigator)
  • Ittner, Arne (Chief Investigator)
  • Lee, Albert (Chief Investigator)
  • Mather, Karen A. (Chief Investigator)
  • Thompson, Elizabeth (Associate Investigator)
  • Burgio, Gaetan (Associate Investigator)

Project: Research

Project Details


Frontotemporal dementia (FTD), a common cause of presenile dementia, is characterised by behavioural and/or language changes and progressive cognitive deficits arising from neuronal degeneration. FTD shows significant clinical and genetic overlap with motor neuron disease (MND), a rapidly progressive neurodegenerative disorder. Our understanding of FTD and MND has
been greatly enhanced by the identification of the genes that underlie the neurodegenerative process. There is no medication for FTD and the current MND treatment extends life by only a few months. There is therefore a critical need for new targets and therapies for these fatal disorders.
Positional cloning of a large, multi-generational family with FTD and MND has identified a new disease gene, CYLD. This gene encodes an enzyme involved in autophagy, one of the major processes by which the cells breaks down unwanted or misfolded proteins. Loss-of-function mutations in CYLD abrogate CYLD enzyme activity and lead to skin tumour disorders. In contrast, the M719V mutation we have identified in the FTD-MND family increases CYLD enzyme activity.
Effective start/end date1/01/1831/12/21