Journal article

X-ray fluorescence imaging reveals subcellular biometal disturbances in a childhood neurodegenerative disorder

A Grubman, SA James, J James, C Duncan, I Volitakis, JL Hickey, PJ Crouch, PS Donnelly, KM Kanninen, JR Liddell, SL Cotman, MD de Jonge, AR White

CHEMICAL SCIENCE | ROYAL SOC CHEMISTRY | Published : 2014

Abstract

Biometals such as zinc, iron, copper and calcium play key roles in diverse physiological processes in the brain, but can be toxic in excess. A hallmark of neurodegeneration is a failure of homeostatic mechanisms controlling the concentration and distribution of these elements, resulting in overload, deficiency or mislocalization. A major roadblock to understanding the impact of altered biometal homeostasis in neurodegenerative disease is the lack of rapid, specific and sensitive techniques capable of providing quantitative subcellular information on biometal homeostasis in situ. Recent advances in X-ray fluorescence detectors have provided an opportunity to rapidly measure biometal content a..

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Grants

Awarded by National Health and Medical Research Council of Australia (NHMRC)


Awarded by National Institutes of Health: National Institute of Neurological Disorders Stroke


Awarded by ARC Future Fellowship


Awarded by NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE


Funding Acknowledgements

Parts of this work were performed at the XFM beamline at the Australian Synchrotron, Victoria, Australia. This work was supported by the National Health and Medical Research Council of Australia (NHMRC) [628946] and the National Institutes of Health: National Institute of Neurological Disorders & Stroke [R01NS073813]. ARW is a recipient of an ARC Future Fellowship [FT100100674]. The funding sources had no influence in study design; collection, analysis, and interpretation of data; writing the report; or the decision to submit the report for publication. Patent protection has previously been sought by the University of Melbourne for the use of bis(-thiosemicarbazones) for treatment of diseases. ARW and PSD are co-inventors on this patent application PCT/AU2007/001792, which is the subject of a commercialization contract between the University and a private company. The company has not funded nor contributed to research described in this manuscript.