Journal article

Deregulation of biometal homeostasis: the missing link for neuronal ceroid lipofuscinoses?

Alexandra Grubman, Eveliina Pollari, Clare Duncan, Aphrodite Caragounis, Tea Blom, Irene Volitakis, Andrew Wong, Jonathan Cooper, Peter J Crouch, Jari Koistinaho, Anu Jalanko, Anthony R White, Katja M Kanninen



Neuronal ceroid lipofuscinoses (NCLs), a group of genetically distinct fatal neurodegenerative disorders with no treatment or cure, are clinically characterised by progressive motor and visual decline leading to premature death. While the underlying pathological mechanisms are yet to be precisely determined, the diseases share several common features including inflammation, lysosomal lipofuscin deposits and lipid abnormalities. An important hallmark of most common neurodegenerative disorders including Alzheimer's, Parkinson's and motor neuron diseases is deregulation of biologically active metal homeostasis. Metals such as zinc, copper and iron are critical enzyme cofactors and are important..

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University of Melbourne Researchers


Awarded by Sigrid Juselius Foundation

Awarded by Academy of Finland

Awarded by Australian Research Council (ARC)

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

Funding Acknowledgements

This work was supported by The Sigrid Juselius Foundation [grant number 1512032 to K. M. K]; the Academy of Finland [grant number 135625 to K. M. K]; the Finnish Cultural Foundation [grant to K. M. K]; the Australian Research Council (ARC) [DP110101368]; and National Health and Medical Research Council of Australia (NHMRC) [628946]. A. R. W. is a recipient of an ARC Future Fellowship [FT100100674]. Essi Kaiharju is thanked for the excellent technical assistance with mouse experiments. The funding sources had no influence in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication. AG, KMK, ARW designed experiments. AG, EP, CD, AC, TB, IV, AW, AJ, JC performed experiments. AG, EP, KMK, IV analysed the data. AG and KMK wrote the manuscript. PJC, JK, AJ, JC, ARW, provided reagents. KMK, ARW, PJC, JK, TB, AW provided critical revisions of the manuscript.