Journal article
The novel compound PBT434 prevents iron mediated neurodegeneration and alpha-synuclein toxicity in multiple models of Parkinson's disease
DI Finkelstein, JL Billings, PA Adlard, S Ayton, A Sedjahtera, CL Masters, S Wilkins, DM Shackleford, SA Charman, W Bal, IA Zawisza, E Kurowska, AL Gundlach, S Ma, AI Bush, DJ Hare, PA Doble, S Crawford, ECL Gautier, J Parsons Show all
Acta Neuropathologica Communications | BMC | Published : 2017
Abstract
Elevated iron in the SNpc may play a key role in Parkinson's disease (PD) neurodegeneration since drug candidates with high iron affinity rescue PD animal models, and one candidate, deferirpone, has shown efficacy recently in a phase two clinical trial. However, strong iron chelators may perturb essential iron metabolism, and it is not yet known whether the damage associated with iron is mediated by a tightly bound (eg ferritin) or lower-affinity, labile, iron pool. Here we report the preclinical characterization of PBT434, a novel quinazolinone compound bearing a moderate affinity metal-binding motif, which is in development for Parkinsonian conditions. In vitro, PBT434 was far less potent ..
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Funding Acknowledgements
The work was supported by funds from the National Health and Medical Research Council, The Australian Research Council, The Michael J. Fox Foundation for Parkinson's Disease Research, Parkinsons UK and Prana Biotechnology Ltd. The Florey Institute of Neuroscience and Mental Health acknowledge the strong support from the Victorian Government and in particular the funding from the Operational Infrastructure Support Grant.