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 | |
| State | Published - Feb 2020 |
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Keywords
- Aggregation
- Alzheimer's
- Amyloid
- DJ-1
- Parkinson's
PubMed: MeSH publication types
- Journal Article
Cite this
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
}
TY - JOUR
T1 - DJ-1 can form β-sheet structured aggregates that co-localize with pathological amyloid deposits
AU - Solti, Katalin
AU - Kuan, Wei Li
AU - Fórizs, Balázs
AU - Kustos, Gergely
AU - Mihály, Judith
AU - Varga, Zoltán
AU - Herberth, Balázs
AU - Moravcsik, Éva
AU - Kiss, Róbert
AU - Kárpáti, Manuela
AU - Mikes, Anna
AU - Zhao, Yanyan
AU - Imre, Tímea
AU - Rochet, Jean Christophe
AU - Aigbirhio, Franklin
AU - Williams-Gray, Caroline H.
AU - Barker, Roger A.
AU - Tóth, Gergely
PY - 2020/2
Y1 - 2020/2
N2 - 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.
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.
KW - Aggregation
KW - Alzheimer's
KW - Amyloid
KW - DJ-1
KW - Parkinson's
UR - http://www.scopus.com/inward/record.url?scp=85074968402&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85074968402&partnerID=8YFLogxK
U2 - 10.1016/j.nbd.2019.104629
DO - 10.1016/j.nbd.2019.104629
M3 - Article
C2 - 31669752
AN - SCOPUS:85074968402
VL - 134
JO - Neurobiology of Disease
JF - Neurobiology of Disease
SN - 0969-9961
M1 - 104629
ER -