Poul Henning Jensen

DJ-1 interactions with α-synuclein attenuate aggregation and cellular toxicity in models of Parkinson's disease

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Standard

DJ-1 interactions with α-synuclein attenuate aggregation and cellular toxicity in models of Parkinson's disease. / Zondler, L; Miller-Fleming, L; Repici, M; Gonçalves, S; Tenreiro, S; Rosado-Ramos, R; Betzer, Cristine; Straatman, K R; Jensen, Poul Henning; Giorgini, F; Outeiro, T F.

In: Cell Death & Disease, Vol. 5, 2014, p. e1350.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

Zondler, L, Miller-Fleming, L, Repici, M, Gonçalves, S, Tenreiro, S, Rosado-Ramos, R, Betzer, C, Straatman, KR, Jensen, PH, Giorgini, F & Outeiro, TF 2014, 'DJ-1 interactions with α-synuclein attenuate aggregation and cellular toxicity in models of Parkinson's disease', Cell Death & Disease, vol. 5, pp. e1350. https://doi.org/10.1038/cddis.2014.307

APA

Zondler, L., Miller-Fleming, L., Repici, M., Gonçalves, S., Tenreiro, S., Rosado-Ramos, R., ... Outeiro, T. F. (2014). DJ-1 interactions with α-synuclein attenuate aggregation and cellular toxicity in models of Parkinson's disease. Cell Death & Disease, 5, e1350. https://doi.org/10.1038/cddis.2014.307

CBE

Zondler L, Miller-Fleming L, Repici M, Gonçalves S, Tenreiro S, Rosado-Ramos R, Betzer C, Straatman KR, Jensen PH, Giorgini F, Outeiro TF. 2014. DJ-1 interactions with α-synuclein attenuate aggregation and cellular toxicity in models of Parkinson's disease. Cell Death & Disease. 5:e1350. https://doi.org/10.1038/cddis.2014.307

MLA

Vancouver

Zondler L, Miller-Fleming L, Repici M, Gonçalves S, Tenreiro S, Rosado-Ramos R et al. DJ-1 interactions with α-synuclein attenuate aggregation and cellular toxicity in models of Parkinson's disease. Cell Death & Disease. 2014;5:e1350. https://doi.org/10.1038/cddis.2014.307

Author

Zondler, L ; Miller-Fleming, L ; Repici, M ; Gonçalves, S ; Tenreiro, S ; Rosado-Ramos, R ; Betzer, Cristine ; Straatman, K R ; Jensen, Poul Henning ; Giorgini, F ; Outeiro, T F. / DJ-1 interactions with α-synuclein attenuate aggregation and cellular toxicity in models of Parkinson's disease. In: Cell Death & Disease. 2014 ; Vol. 5. pp. e1350.

Bibtex

@article{631d6f69b91b4dde88044f347df4f95d,
title = "DJ-1 interactions with α-synuclein attenuate aggregation and cellular toxicity in models of Parkinson's disease",
abstract = "Parkinson's disease (PD) is a devastating neurodegenerative disorder characterized by the loss of neurons in the substantia nigra pars compacta and the presence of Lewy bodies in surviving neurons. These intracellular protein inclusions are primarily composed of misfolded α-synuclein (aSyn), which has also been genetically linked to familial and sporadic forms of PD. DJ-1 is a small ubiquitously expressed protein implicated in several pathways associated with PD pathogenesis. Although mutations in the gene encoding DJ-1 lead to familial early-onset PD, the exact mechanisms responsible for its role in PD pathogenesis are still elusive. Previous work has found that DJ-1 - which has protein chaperone-like activity - modulates aSyn aggregation. Here, we investigated possible physical interactions between aSyn and DJ-1 and any consequent functional and pathological relevance. We found that DJ-1 interacts directly with aSyn monomers and oligomers in vitro, and that this also occurs in living cells. Notably, several PD-causing mutations in DJ-1 constrain this interaction. In addition, we found that overexpression of DJ-1 reduces aSyn dimerization, whereas mutant forms of DJ-1 impair this process. Finally, we found that human DJ-1 as well as yeast orthologs of DJ-1 reversed aSyn-dependent cellular toxicity in Saccharomyces cerevisiae. Taken together, these data suggest that direct interactions between DJ-1 and aSyn constitute the basis for a neuroprotective mechanism and that familial mutations in DJ-1 may contribute to PD by disrupting these interactions.",
author = "L Zondler and L Miller-Fleming and M Repici and S Gon{\cc}alves and S Tenreiro and R Rosado-Ramos and Cristine Betzer and Straatman, {K R} and Jensen, {Poul Henning} and F Giorgini and Outeiro, {T F}",
year = "2014",
doi = "10.1038/cddis.2014.307",
language = "English",
volume = "5",
pages = "e1350",
journal = "Cell Death & Disease",
issn = "2041-4889",
publisher = "Nature Publishing Group",

}

RIS

TY - JOUR

T1 - DJ-1 interactions with α-synuclein attenuate aggregation and cellular toxicity in models of Parkinson's disease

AU - Zondler, L

AU - Miller-Fleming, L

AU - Repici, M

AU - Gonçalves, S

AU - Tenreiro, S

AU - Rosado-Ramos, R

AU - Betzer, Cristine

AU - Straatman, K R

AU - Jensen, Poul Henning

AU - Giorgini, F

AU - Outeiro, T F

PY - 2014

Y1 - 2014

N2 - Parkinson's disease (PD) is a devastating neurodegenerative disorder characterized by the loss of neurons in the substantia nigra pars compacta and the presence of Lewy bodies in surviving neurons. These intracellular protein inclusions are primarily composed of misfolded α-synuclein (aSyn), which has also been genetically linked to familial and sporadic forms of PD. DJ-1 is a small ubiquitously expressed protein implicated in several pathways associated with PD pathogenesis. Although mutations in the gene encoding DJ-1 lead to familial early-onset PD, the exact mechanisms responsible for its role in PD pathogenesis are still elusive. Previous work has found that DJ-1 - which has protein chaperone-like activity - modulates aSyn aggregation. Here, we investigated possible physical interactions between aSyn and DJ-1 and any consequent functional and pathological relevance. We found that DJ-1 interacts directly with aSyn monomers and oligomers in vitro, and that this also occurs in living cells. Notably, several PD-causing mutations in DJ-1 constrain this interaction. In addition, we found that overexpression of DJ-1 reduces aSyn dimerization, whereas mutant forms of DJ-1 impair this process. Finally, we found that human DJ-1 as well as yeast orthologs of DJ-1 reversed aSyn-dependent cellular toxicity in Saccharomyces cerevisiae. Taken together, these data suggest that direct interactions between DJ-1 and aSyn constitute the basis for a neuroprotective mechanism and that familial mutations in DJ-1 may contribute to PD by disrupting these interactions.

AB - Parkinson's disease (PD) is a devastating neurodegenerative disorder characterized by the loss of neurons in the substantia nigra pars compacta and the presence of Lewy bodies in surviving neurons. These intracellular protein inclusions are primarily composed of misfolded α-synuclein (aSyn), which has also been genetically linked to familial and sporadic forms of PD. DJ-1 is a small ubiquitously expressed protein implicated in several pathways associated with PD pathogenesis. Although mutations in the gene encoding DJ-1 lead to familial early-onset PD, the exact mechanisms responsible for its role in PD pathogenesis are still elusive. Previous work has found that DJ-1 - which has protein chaperone-like activity - modulates aSyn aggregation. Here, we investigated possible physical interactions between aSyn and DJ-1 and any consequent functional and pathological relevance. We found that DJ-1 interacts directly with aSyn monomers and oligomers in vitro, and that this also occurs in living cells. Notably, several PD-causing mutations in DJ-1 constrain this interaction. In addition, we found that overexpression of DJ-1 reduces aSyn dimerization, whereas mutant forms of DJ-1 impair this process. Finally, we found that human DJ-1 as well as yeast orthologs of DJ-1 reversed aSyn-dependent cellular toxicity in Saccharomyces cerevisiae. Taken together, these data suggest that direct interactions between DJ-1 and aSyn constitute the basis for a neuroprotective mechanism and that familial mutations in DJ-1 may contribute to PD by disrupting these interactions.

U2 - 10.1038/cddis.2014.307

DO - 10.1038/cddis.2014.307

M3 - Journal article

C2 - 25058424

VL - 5

SP - e1350

JO - Cell Death & Disease

JF - Cell Death & Disease

SN - 2041-4889

ER -