Journal article
Ferroptosis mediates selective motor neuron death in amyotrophic lateral sclerosis
T Wang, D Tomas, ND Perera, B Cuic, S Luikinga, A Viden, SK Barton, CA McLean, AL Samson, A Southon, AI Bush, JM Murphy, BJ Turner
Cell Death and Differentiation | Published : 2022
Abstract
Amyotrophic lateral sclerosis (ALS) is caused by selective degeneration of motor neurons in the brain and spinal cord; however, the primary cell death pathway(s) mediating motor neuron demise remain elusive. We recently established that necroptosis, an inflammatory form of regulated cell death, was dispensable for motor neuron death in a mouse model of ALS, implicating other forms of cell death. Here, we confirm these findings in ALS patients, showing a lack of expression of key necroptotic effector proteins in spinal cords. Rather, we uncover evidence for ferroptosis, a recently discovered iron-dependent form of regulated cell death, in ALS. Depletion of glutathione peroxidase 4 (GPX4), an ..
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Awarded by Parkinson’s Victoria
Funding Acknowledgements
Funding for this project was provided by the Angie Cunningham FightMND PhD Scholarship and Grant (TW, BJT), Australian NHMRC (Fellowship 1137024 to BJT; Grant 2002965 to ALS; Fellowship 1172929 and IRIISS 9000653 to JMM), Rebecca L. Cooper Al & Val Rosenstrauss Medical Research Fellowship (SKB) and Stafford Fox Medical Research Foundation (BJT). Human spinal cord tissues were received from the Victorian Brain Bank, supported by The Florey, The Alfred, Victorian Institute of Forensic Medicine and Coroners Court of Victoria and funded in part by Parkinson's Victoria, MND Victoria, FightMND, Yulgilbar Foundation and Ian and Maria Cootes. The Florey Institute of Neuroscience & Mental Health and Walter & Eliza Hall Institute acknowledge Victorian Government Operational Infrastructure Support.