DJ-1 can form β-sheet structured aggregates that co-localize with pathological amyloid deposits

Katalin Solti; Wei Li Kuan; Balázs Fórizs; Gergely Kustos; Judith Mihály; Zoltán Varga; Balázs Herberth; Éva Moravcsik; Róbert Kiss; Manuela Kárpáti; Anna Mikes; Yanyan Zhao; Tímea Imre; Jean Christophe Rochet; Franklin Aigbirhio; Caroline H. Williams-Gray; Roger A. Barker; Gergely Tóth

doi:10.1016/j.nbd.2019.104629

DJ-1 can form β-sheet structured aggregates that co-localize with pathological amyloid deposits

Katalin Solti, Wei Li Kuan, Balázs Fórizs, Gergely Kustos, Judith Mihály, Zoltán Varga, Balázs Herberth, Éva Moravcsik, Róbert Kiss, Manuela Kárpáti, Anna Mikes, Yanyan Zhao, Tímea Imre, Jean Christophe Rochet, Franklin Aigbirhio, Caroline H. Williams-Gray, Roger A. Barker, Gergely Tóth

Research output: Contribution to journal › Article

1 Scopus citations

Abstract

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 β-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.

Original language	English (US)
Article number	104629
Journal	Neurobiology of Disease
Volume	134
DOIs	https://doi.org/10.1016/j.nbd.2019.104629
State	Published - Feb 2020
Externally published	Yes

Keywords

Aggregation
Alzheimer's
Amyloid
DJ-1
Parkinson's

PubMed: MeSH publication types

Journal Article
Research Support, Non-U.S. Gov't

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Solti, K., Kuan, W. L., Fórizs, B., Kustos, G., Mihály, J., Varga, Z., Herberth, B., Moravcsik, É., Kiss, R., Kárpáti, M., Mikes, A., Zhao, Y., Imre, T., Rochet, J. C., Aigbirhio, F., Williams-Gray, C. H., Barker, R. A., & Tóth, G. (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

DJ-1 can form β-sheet structured aggregates that co-localize with pathological amyloid deposits. / Solti, Katalin; Kuan, Wei Li; Fórizs, Balázs; Kustos, Gergely; Mihály, Judith; Varga, Zoltán; Herberth, Balázs; Moravcsik, Éva; Kiss, Róbert; Kárpáti, Manuela; Mikes, Anna; Zhao, Yanyan; Imre, Tímea; Rochet, Jean Christophe; Aigbirhio, Franklin; Williams-Gray, Caroline H.; Barker, Roger A.; Tóth, Gergely.

In: Neurobiology of Disease, Vol. 134, 104629, 02.2020.

Research output: Contribution to journal › Article

Solti, K, Kuan, WL, Fórizs, B, Kustos, G, Mihály, J, Varga, Z, Herberth, B, Moravcsik, É, Kiss, R, Kárpáti, M, Mikes, A, Zhao, Y, Imre, T, Rochet, JC, Aigbirhio, F, Williams-Gray, CH, Barker, RA & Tóth, G 2020, 'DJ-1 can form β-sheet structured aggregates that co-localize with pathological amyloid deposits', Neurobiology of Disease, vol. 134, 104629. https://doi.org/10.1016/j.nbd.2019.104629

Solti, Katalin ; Kuan, Wei Li ; Fórizs, Balázs ; Kustos, Gergely ; Mihály, Judith ; Varga, Zoltán ; Herberth, Balázs ; Moravcsik, Éva ; Kiss, Róbert ; Kárpáti, Manuela ; Mikes, Anna ; Zhao, Yanyan ; Imre, Tímea ; Rochet, Jean Christophe ; Aigbirhio, Franklin ; Williams-Gray, Caroline H. ; Barker, Roger A. ; Tóth, Gergely. / DJ-1 can form β-sheet structured aggregates that co-localize with pathological amyloid deposits. In: Neurobiology of Disease. 2020 ; Vol. 134.

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abstract = "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 β-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.",

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AU - Rochet, Jean Christophe

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AB - 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 β-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.

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