Zinc affects the proteolytic stability of Apolipoprotein E in an isoform-dependent way
He Xu, Veer B Gupta, Ian J Martins, Ralph N Martins, Christopher J Fowler, Ashley I Bush, David I Finkelstein, Paul A Adlard
NEUROBIOLOGY OF DISEASE | ACADEMIC PRESS INC ELSEVIER SCIENCE | Published : 2015
The pathological role of zinc in Alzheimer's disease (AD) is not yet fully elucidated, but there is strong evidence that zinc homeostasis is impaired in the AD brain and that this contributes to disease pathogenesis. In this study we examined the effects of zinc on the proteolysis of synthetic Apolipoprotein E (ApoE), a protein whose allelic variants differentially contribute to the onset/progression of disease. We have demonstrated that zinc promotes the proteolysis (using plasma kallikrein, thrombin and chymotrypsin) of synthetic ApoE in an isoform-specific way (E4>E2 and E3), resulting in more ApoE fragments, particularly for ApoE4. In the absence of exogenous proteases there was no effec..View full abstract
PAA is supported by an ARC Future Fellowship. In addition, 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. He Xu is supported by a University of Melbourne Scholarship. We wish to thank the donors of blood samples, who were participants in the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing (AIBL) (http://www.aibl.csiro.au/). In addition, we acknowledge the contribution of Dr Alan Rembach (deceased) both to facilitating the provision of human samples for this study, and to his larger role with AIBL.