Skip to main content
Navigate back to homepage
Open search bar.
Open main navigation menu

Main navigation

  • Study
    UCL Portico statue
    Study at UCL

    Being a student at UCL is about so much more than just acquiring knowledge. Studying here gives you the opportunity to realise your potential as an individual, and the skills and tools to thrive.

    • Undergraduate courses
    • Graduate courses
    • Short courses
    • Study abroad
    • Centre for Languages & International Education
  • Research
    Tree-of-Life-MehmetDavrandi-UCL-EastmanDentalInstitute-042_2017-18-800x500-withborder (1)
    Research at UCL

    Find out more about what makes UCL research world-leading, how to access UCL expertise, and teams in the Office of the Vice-Provost (Research, Innovation and Global Engagement).

    • Engage with us
    • Explore our Research
    • Initiatives and networks
    • Research news
  • Engage
    UCL Print room
    Engage with UCL

    Discover the many ways you can connect with UCL, and how we work with industry, government and not-for-profit organisations to tackle tough challenges.

    • Alumni
    • Business partnerships and collaboration
    • Global engagement
    • News and Media relations
    • Public Policy
    • Schools and priority groups
    • Visit us
  • About
    UCL welcome quad
    About UCL

    Founded in 1826 in the heart of London, UCL is London's leading multidisciplinary university, with more than 16,000 staff and 50,000 students from 150 different countries.

    • Who we are
    • Faculties
    • Governance
    • President and Provost
    • Strategy
  • Active parent page: Brain Sciences
    • Study
    • Research
    • About the Faculty
    • Institutes and Divisions
    • Active parent page: News and Events
    • Contact

New mechanism arising from mutant protein could shed light on causes of neurodegenerative disease

Breadcrumb trail

  • Brain Sciences
  • News and Events

Faculty menu

  • Current page: Faculty news
  • Events

A research team led by Dr Pietro Fratta, Professor Elizabeth Fisher (both UCL Institute of Neurology), and Dr Abraham Acevedo Arozena (Hospital Universitario de Canaria, Spain) has discovered a new mechanism arising from a mutant protein, TDP-43, which causes ‘skipping’ of normal regions of other gene products. 

TDP-43 is a protein which is deposited in many neurodegenerative diseases including motor neuron disease (MND, also known as amyotrophic lateral sclerosis or ALS) and frontotemporal dementia (FTD). Some MND is caused by mutations in the gene which encodes TDP-43, but the link between gene mutation and the resulting neuronal death remains to be determined.

This joint research team studied mouse models that had progressive motor neuron degeneration – because the mutant TDP-43 protein was present. They identified a mechanism whereby TDP-43 causes skipping over some normal regions of DNA in other gene products.

This skipping has been described by the researchers as ‘skiptic exon’ events. An exon is any part of a gene which contains information required to encode a protein.

Skiptic exon events are also present in cells from human patients with MND. These findings therefore provide insight into how TDP-43 causes neurodegenerative disease in humans.

Professor Fisher commented: “This is another piece in the jigsaw as to how this protein causes human neurodegeneration.” 

Dr Fratta said, ‘This takes us further into understanding neurodegeneration in ALS/MND.’

Dr Acevedo Arozena commented: “It gives us novel models to particularly study what's going wrong with this protein at the crucial early disease stages.”

Related

  • Full journal article, 'Mice with endogenous TDP‐43 mutations exhibit gain of splicing function and characteristics of amyotrophic lateral sclerosis,' EMBO Journal
  • Hospital Universitario de Canaria
  • Professor Elizabeth Fisher's UCL IRIS profile

UCL footer

Visit

  • Bloomsbury Theatre and Studio
  • Library, Museums and Collections
  • UCL Maps
  • UCL Shop
  • Contact UCL

Students

  • Accommodation
  • Current Students
  • Moodle
  • Students' Union

Staff

  • Inside UCL
  • Staff Intranet
  • Work at UCL
  • Human Resources

UCL social media menu

  • Link to Soundcloud
  • Link to Flickr
  • Link to TikTok
  • Link to Youtube
  • Link to Instagram
  • Link to Facebook
  • Link to Twitter

University College London, Gower Street, London, WC1E 6BT

Tel: +44 (0) 20 7679 2000

© 2025 UCL

Essential

  • Disclaimer
  • Freedom of Information
  • Accessibility
  • Cookies
  • Privacy
  • Slavery statement
  • Log in