DJ-1 can form β-sheet structured aggregates that co-localize with pathological amyloid deposits.
Neurobiology of disease
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Solti, K., Kuan, W., Fórizs, B., Kustos, G., Mihály, J., Varga, Z., Herberth, B., et al. (2020). DJ-1 can form β-sheet structured aggregates that co-localize with pathological amyloid deposits.. Neurobiology of disease, 134 104629. https://doi.org/10.1016/j.nbd.2019.104629
The loss of native function of the DJ-1 protein has been linked to the development of Parkinson’s (PD) and other neurodegenerative diseases. Here we show that DJ-1 aggregates into -sheet structured soluble and fibrillar aggregates in vitro under physiological conditions and that this process is promoted by the oxidation of its catalytic Cys106 residue. This aggregation resulted in the loss of its native biochemical glyoxalase function and in addition oxidized DJ-1 aggregates were observed to localize within Lewy bodies, neurofibrillary tangles and amyloid plaques in human PD and Alzheimer’s (AD) patients’ post-mortem brain tissue. These findings suggest that the aggregation of DJ-1 may be a critical player in the development of the pathology of PD and AD and demonstrate that loss of DJ-1 function can happen through DJ-1 aggregation. This could then contribute to AD and PD disease onset and progression.
G.T. thanks the Hungarian Brain Research Program (2017-1.2.1-NKP-2017-00002) for funding and the NIHR Cambridge Biomedical Research Centre and Unit in Dementia (UK) for salary support for Y. Z. R.A.B. and C.H.W.G. are supported by the NIHR Cambridge Biomedical Research Centre. R. A. B. is supported by the Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute and is an NIHR Senior Investigator.
Department of Health (via National Institute for Health Research (NIHR)) (NF-SI-0616-10011)
Cambridge University Hospitals NHS Foundation Trust (CUH) (146281)
MEDICAL RESEARCH COUNCIL (MR/M009041/1)
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External DOI: https://doi.org/10.1016/j.nbd.2019.104629
This record's URL: https://www.repository.cam.ac.uk/handle/1810/297423
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Licence URL: https://creativecommons.org/licenses/by-nc-nd/4.0/