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EMAIL ajw69@cam.ac.uk
College Wolfson College
Department
  • Clinical Neurosciences
    • School
  • Clinical Medicine
    • Institute
  • MRC Mitochondrial Biology Unit
    • Research Theme Beyond the Neuron Lifelong Brain Development and Brain Ageing
    Research Focus

    Keywords

  • Ageing
  • Neurodegeneration
  • Parkinson's Disease
  • Motor Neuron Disease
  • Dementia
  • Mitochondria
  • Mitochondrial Dysfunction
  • Animal Models

    • Clinical Conditions

  • Parkinson's disease
  • Motor neurone disease
  • Dementia

    • Equipment & Techniques

  • Behavioural analysis
  • Confocal microscopy
  • Cell culture
  • Microscopy
  • Immunohistochemistry
  • Calcium imaging

    • Science Culture

  • CamBRAIN
  • Equality, Diversity, Inclusion and Wellbeing
  • Open Access
  • Public Engagement
  • Public Outreach
  • Widening Participation

    • Back

    Dr Alex Whitworth

    University Position
    Programme Leader

    Interests

    My lab is interested in understanding the mechanisms of mitochondrial homeostasis in relation to neurodegenerative diseases such as Parkinson's disease and motor neuron disease. We use a combination of the powerful genetic techniques of Drosophila and molecular, cell biology and biochemical approaches in mammalian cells. Insights into these mechanisms will deliver a greater understanding of the role of mitochondrial maintenance in the health and dysfunction of the nervous system in a physiological context and will help guide therapeutic development to combat neurodegenerative diseases.

    Key Publications

    Partial loss of MCU mitigates pathology in vivo across a diverse range of neurodegenerative disease models.

    DOI: http://doi.org/10.1016/j.celrep.2024.113681
    Journal: Cell Rep
    E-pub date: 27 Feb 2024
    Authors: MJ Twyning, R Tufi, TP Gleeson, KM Kolodziej, S Campesan, A Terriente-Felix, L Collins, F De Lazzari, F Giorgini, AJ Whitworth

    Mitochondrial CISD1/Cisd accumulation blocks mitophagy and genetic or pharmacological inhibition rescues neurodegenerative phenotypes in Pink1/parkin models

    DOI: http://doi.org/10.1186/s13024-024-00701-3
    Journal: Mol Neurodegener
    E-pub date: 25 Jan 2024
    Authors: A Martinez, A Sanchez-Martinez, JT Pickering, MJ Twyning, A Terriente-Felix, P-L Chen, C-H Chen, AJ Whitworth

    FBXO7/ntc and USP30 antagonistically set the ubiquitination threshold for basal mitophagy and provide a target for Pink1 phosphorylation in vivo.

    DOI: http://doi.org/10.1371/journal.pbio.3002244
    Journal: PLoS Biol
    E-pub date: 31 Aug 2023
    Authors: A Sanchez-Martinez, A Martinez, AJ Whitworth

    Parkin drives pS65-Ub turnover independently of canonical autophagy in Drosophila.

    DOI: http://doi.org/10.15252/embr.202153552
    Journal: EMBO Rep
    E-pub date: 6 Dec 2022
    Authors: JL Usher, A Sanchez-Martinez, A Terriente-Felix, P-L Chen, JJ Lee, C-H Chen, AJ Whitworth

    Comprehensive Genetic Characterization of Mitochondrial Ca2+ Uniporter Components Reveals Their Different Physiological Requirements In Vivo.

    DOI: http://doi.org/10.1016/j.celrep.2019.04.033
    Journal: Cell Rep
    E-pub date: 30 Apr 2019
    Authors: R Tufi, TP Gleeson, S von Stockum, VL Hewitt, JJ Lee, A Terriente-Felix, A Sanchez-Martinez, E Ziviani, AJ Whitworth

    Publications

    Activation of the Keap1/Nrf2 pathway suppresses mitochondrial dysfunction, oxidative stress, and motor phenotypes inC9orf72ALS/FTD models

    DOI: http://doi.org/10.26508/lsa.202402853
    Journal: Life Sci Alliance
    E-pub date: 1 Sep 2024
    Authors: WH Au, L Miller-Fleming, A Sanchez-Martinez, JAK Lee, MJ Twyning, HA Prag, L Raik, SP Allen, PJ Shaw, L Ferraiuolo, H Mortiboys, AJ Whitworth

    Analysis of Mitophagy Reporters in Drosophila.

    DOI: http://doi.org/10.1007/978-1-0716-4067-8_7
    Journal: Methods Mol Biol
    E-pub date: 1 Aug 2024
    Authors: A Sanchez-Martinez, A Martinez, AJ Whitworth

    USP8 inhibition promotes Parkin-independent mitophagy in theDrosophilabrain and in human neurons

    DOI: http://doi.org/10.1101/2023.01.30.526170
    Journal:
    E-pub date: 1 Aug 2023
    Authors: S Mauri, G Bernardo, A Martinez, M Favaro, M Trevisan, G Cobraiville, M Fillet, F Caicci, A Whitworth, E Ziviani

    Activation of the Keap1/Nrf2 pathway suppresses mitochondrial dysfunction in C9orf72 ALS/FTD in vivo models and patient iNeurons

    DOI: http://doi.org/10.1101/2023.10.02.560439
    Journal:
    E-pub date: 1 Aug 2023
    Authors: WH Au, L Miller-Fleming, A Sanchez-Martinez, J Lee, M Twyning, H Prag, S Granger, K Roome, L Ferraiuolo, H Mortiboys, A Whitworth

    A cell-penetrant peptide blocking C9ORF72-repeat RNA nuclear export reduces the neurotoxic effects of dipeptide repeat proteins.

    DOI: http://doi.org/10.1126/scitranslmed.abo3823
    Journal: Sci Transl Med
    E-pub date: 1 Mar 2023
    Authors: LM Castelli, Y-H Lin, A Sanchez-Martinez, A Gül, K Mohd Imran, A Higginbottom, SK Upadhyay, NM Márkus, R Rua Martins, J Cooper-Knock, C Montmasson, R Cohen, A Walton, CS Bauer, KJ De Vos, RJ Mead, M Azzouz, C Dominguez, L Ferraiuolo, PJ Shaw, AJ Whitworth, GM Hautbergue

    Antioxidant Therapy in Parkinson’s Disease: Insights from Drosophila melanogaster.

    DOI: http://doi.org/10.3390/antiox9010052
    Journal: Antioxidants (Basel)
    E-pub date: 7 Jan 2020
    Authors: F De Lazzari, F Sandrelli, AJ Whitworth, M Bisaglia

    Axonal transport defects are a common phenotype in Drosophila models of ALS.

    DOI: http://doi.org/10.1093/hmg/ddw105
    Journal: Hum Mol Genet
    E-pub date: 15 Jun 2016
    Authors: KR Baldwin, VK Godena, VL Hewitt, AJ Whitworth