Alpha-synuclein aggregates activate calcium pump SERCA leading to calcium dysregulation

Research output: Contribution to journalJournal articleResearchpeer-review

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Alpha-synuclein aggregates activate calcium pump SERCA leading to calcium dysregulation. / Betzer, Cristine; Lassen, Louise Berkhoudt; Olsen, Anders; Kofoed, Rikke Hahn; Reimer, Lasse; Gregersen, Emil; Zheng, Jin; Calì, Tito; Gai, Wei Ping; Chen, Tong; Moeller, Arne; Brini, Marisa; Fu, Yuhong; Halliday, Glenda; Brudek, Tomasz; Aznar, Susana; Pakkenberg, Bente; Andersen, Jens Peter; Jensen, Poul Henning.

In: EMBO Reports, Vol. 19, No. 5, e44617, 2018.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Betzer, C, Lassen, LB, Olsen, A, Kofoed, RH, Reimer, L, Gregersen, E, Zheng, J, Calì, T, Gai, WP, Chen, T, Moeller, A, Brini, M, Fu, Y, Halliday, G, Brudek, T, Aznar, S, Pakkenberg, B, Andersen, JP & Jensen, PH 2018, 'Alpha-synuclein aggregates activate calcium pump SERCA leading to calcium dysregulation', EMBO Reports, vol. 19, no. 5, e44617. https://doi.org/10.15252/embr.201744617

APA

Betzer, C., Lassen, L. B., Olsen, A., Kofoed, R. H., Reimer, L., Gregersen, E., Zheng, J., Calì, T., Gai, W. P., Chen, T., Moeller, A., Brini, M., Fu, Y., Halliday, G., Brudek, T., Aznar, S., Pakkenberg, B., Andersen, J. P., & Jensen, P. H. (2018). Alpha-synuclein aggregates activate calcium pump SERCA leading to calcium dysregulation. EMBO Reports, 19(5), [e44617]. https://doi.org/10.15252/embr.201744617

Vancouver

Betzer C, Lassen LB, Olsen A, Kofoed RH, Reimer L, Gregersen E et al. Alpha-synuclein aggregates activate calcium pump SERCA leading to calcium dysregulation. EMBO Reports. 2018;19(5). e44617. https://doi.org/10.15252/embr.201744617

Author

Betzer, Cristine ; Lassen, Louise Berkhoudt ; Olsen, Anders ; Kofoed, Rikke Hahn ; Reimer, Lasse ; Gregersen, Emil ; Zheng, Jin ; Calì, Tito ; Gai, Wei Ping ; Chen, Tong ; Moeller, Arne ; Brini, Marisa ; Fu, Yuhong ; Halliday, Glenda ; Brudek, Tomasz ; Aznar, Susana ; Pakkenberg, Bente ; Andersen, Jens Peter ; Jensen, Poul Henning. / Alpha-synuclein aggregates activate calcium pump SERCA leading to calcium dysregulation. In: EMBO Reports. 2018 ; Vol. 19, No. 5.

Bibtex

@article{1ca6730eed9b4b4d8b9d8dbf099b0d56,
title = "Alpha-synuclein aggregates activate calcium pump SERCA leading to calcium dysregulation",
abstract = "Aggregation of α-synuclein is a hallmark of Parkinson's disease and dementia with Lewy bodies. We here investigate the relationship between cytosolic Ca2+ and α-synuclein aggregation. Analyses of cell lines and primary culture models of α-synuclein cytopathology reveal an early phase with reduced cytosolic Ca2+ levels followed by a later Ca2+ increase. Aggregated but not monomeric α-synuclein binds to and activates SERCA in vitro, and proximity ligation assays confirm this interaction in cells. The SERCA inhibitor cyclopiazonic acid (CPA) normalises both the initial reduction and the later increase in cytosolic Ca2+. CPA protects the cells against α-synuclein-aggregate stress and improves viability in cell models and in Caenorhabditis elegans in vivo. Proximity ligation assays also reveal an increased interaction between α-synuclein aggregates and SERCA in human brains affected by dementia with Lewy bodies. We conclude that α-synuclein aggregates bind SERCA and stimulate its activity. Reducing SERCA activity is neuroprotective, indicating that SERCA and down-stream processes may be therapeutic targets for treating α-synucleinopathies.",
keywords = "aggregation, alpha-synuclein, calcium, endoplasmic reticulum, SERCA",
author = "Cristine Betzer and Lassen, {Louise Berkhoudt} and Anders Olsen and Kofoed, {Rikke Hahn} and Lasse Reimer and Emil Gregersen and Jin Zheng and Tito Cal{\`i} and Gai, {Wei Ping} and Tong Chen and Arne Moeller and Marisa Brini and Yuhong Fu and Glenda Halliday and Tomasz Brudek and Susana Aznar and Bente Pakkenberg and Andersen, {Jens Peter} and Jensen, {Poul Henning}",
year = "2018",
doi = "10.15252/embr.201744617",
language = "English",
volume = "19",
journal = "E M B O Reports",
issn = "1469-221X",
publisher = "Wiley-Blackwell",
number = "5",

}

RIS

TY - JOUR

T1 - Alpha-synuclein aggregates activate calcium pump SERCA leading to calcium dysregulation

AU - Betzer, Cristine

AU - Lassen, Louise Berkhoudt

AU - Olsen, Anders

AU - Kofoed, Rikke Hahn

AU - Reimer, Lasse

AU - Gregersen, Emil

AU - Zheng, Jin

AU - Calì, Tito

AU - Gai, Wei Ping

AU - Chen, Tong

AU - Moeller, Arne

AU - Brini, Marisa

AU - Fu, Yuhong

AU - Halliday, Glenda

AU - Brudek, Tomasz

AU - Aznar, Susana

AU - Pakkenberg, Bente

AU - Andersen, Jens Peter

AU - Jensen, Poul Henning

PY - 2018

Y1 - 2018

N2 - Aggregation of α-synuclein is a hallmark of Parkinson's disease and dementia with Lewy bodies. We here investigate the relationship between cytosolic Ca2+ and α-synuclein aggregation. Analyses of cell lines and primary culture models of α-synuclein cytopathology reveal an early phase with reduced cytosolic Ca2+ levels followed by a later Ca2+ increase. Aggregated but not monomeric α-synuclein binds to and activates SERCA in vitro, and proximity ligation assays confirm this interaction in cells. The SERCA inhibitor cyclopiazonic acid (CPA) normalises both the initial reduction and the later increase in cytosolic Ca2+. CPA protects the cells against α-synuclein-aggregate stress and improves viability in cell models and in Caenorhabditis elegans in vivo. Proximity ligation assays also reveal an increased interaction between α-synuclein aggregates and SERCA in human brains affected by dementia with Lewy bodies. We conclude that α-synuclein aggregates bind SERCA and stimulate its activity. Reducing SERCA activity is neuroprotective, indicating that SERCA and down-stream processes may be therapeutic targets for treating α-synucleinopathies.

AB - Aggregation of α-synuclein is a hallmark of Parkinson's disease and dementia with Lewy bodies. We here investigate the relationship between cytosolic Ca2+ and α-synuclein aggregation. Analyses of cell lines and primary culture models of α-synuclein cytopathology reveal an early phase with reduced cytosolic Ca2+ levels followed by a later Ca2+ increase. Aggregated but not monomeric α-synuclein binds to and activates SERCA in vitro, and proximity ligation assays confirm this interaction in cells. The SERCA inhibitor cyclopiazonic acid (CPA) normalises both the initial reduction and the later increase in cytosolic Ca2+. CPA protects the cells against α-synuclein-aggregate stress and improves viability in cell models and in Caenorhabditis elegans in vivo. Proximity ligation assays also reveal an increased interaction between α-synuclein aggregates and SERCA in human brains affected by dementia with Lewy bodies. We conclude that α-synuclein aggregates bind SERCA and stimulate its activity. Reducing SERCA activity is neuroprotective, indicating that SERCA and down-stream processes may be therapeutic targets for treating α-synucleinopathies.

KW - aggregation

KW - alpha-synuclein

KW - calcium

KW - endoplasmic reticulum

KW - SERCA

U2 - 10.15252/embr.201744617

DO - 10.15252/embr.201744617

M3 - Journal article

C2 - 29599149

AN - SCOPUS:85044500745

VL - 19

JO - E M B O Reports

JF - E M B O Reports

SN - 1469-221X

IS - 5

M1 - e44617

ER -

ID: 213961802