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Daniel Otzen

The neural chaperone proSAAS blocks α-synuclein fibrillation and neurotoxicity

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Standard

The neural chaperone proSAAS blocks α-synuclein fibrillation and neurotoxicity. / Jarvela, Timothy S; Lam, Hoa A; Helwig, Michael et al.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 113, No. 32, 25.07.2016.

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

Harvard

Jarvela, TS, Lam, HA, Helwig, M, Lorenzen, N, Otzen, DE, McLean, PJ, Maidment, NT & Lindberg, I 2016, 'The neural chaperone proSAAS blocks α-synuclein fibrillation and neurotoxicity', Proceedings of the National Academy of Sciences of the United States of America, vol. 113, no. 32. https://doi.org/10.1073/pnas.1601091113

APA

Jarvela, T. S., Lam, H. A., Helwig, M., Lorenzen, N., Otzen, D. E., McLean, P. J., Maidment, N. T., & Lindberg, I. (2016). The neural chaperone proSAAS blocks α-synuclein fibrillation and neurotoxicity. Proceedings of the National Academy of Sciences of the United States of America, 113(32). https://doi.org/10.1073/pnas.1601091113

CBE

Jarvela TS, Lam HA, Helwig M, Lorenzen N, Otzen DE, McLean PJ, Maidment NT, Lindberg I. 2016. The neural chaperone proSAAS blocks α-synuclein fibrillation and neurotoxicity. Proceedings of the National Academy of Sciences of the United States of America. 113(32). https://doi.org/10.1073/pnas.1601091113

MLA

Jarvela, Timothy S et al. "The neural chaperone proSAAS blocks α-synuclein fibrillation and neurotoxicity". Proceedings of the National Academy of Sciences of the United States of America. 2016. 113(32). https://doi.org/10.1073/pnas.1601091113

Vancouver

Jarvela TS, Lam HA, Helwig M, Lorenzen N, Otzen DE, McLean PJ et al. The neural chaperone proSAAS blocks α-synuclein fibrillation and neurotoxicity. Proceedings of the National Academy of Sciences of the United States of America. 2016 Jul 25;113(32). doi: 10.1073/pnas.1601091113

Author

Jarvela, Timothy S ; Lam, Hoa A ; Helwig, Michael et al. / The neural chaperone proSAAS blocks α-synuclein fibrillation and neurotoxicity. In: Proceedings of the National Academy of Sciences of the United States of America. 2016 ; Vol. 113, No. 32.

Bibtex

@article{7ba822e0ba6c402397b8213e0299b1b9,
title = "The neural chaperone proSAAS blocks α-synuclein fibrillation and neurotoxicity",
abstract = "Emerging evidence strongly suggests that chaperone proteins are cytoprotective in neurodegenerative proteinopathies involving protein aggregation; for example, in the accumulation of aggregated α-synuclein into the Lewy bodies present in Parkinson's disease. Of the various chaperones known to be associated with neurodegenerative disease, the small secretory chaperone known as proSAAS (named after four residues in the amino terminal region) has many attractive properties. We show here that proSAAS, widely expressed in neurons throughout the brain, is associated with aggregated synuclein deposits in the substantia nigra of patients with Parkinson's disease. Recombinant proSAAS potently inhibits the fibrillation of α-synuclein in an in vitro assay; residues 158-180, containing a largely conserved element, are critical to this bioactivity. ProSAAS also exhibits a neuroprotective function; proSAAS-encoding lentivirus blocks α-synuclein-induced cytotoxicity in primary cultures of nigral dopaminergic neurons, and recombinant proSAAS blocks α-synuclein-induced cytotoxicity in SH-SY5Y cells. Four independent proteomics studies have previously identified proSAAS as a potential cerebrospinal fluid biomarker in various neurodegenerative diseases. Coupled with prior work showing that proSAAS blocks β-amyloid aggregation into fibrils, this study supports the idea that neuronal proSAAS plays an important role in proteostatic processes. ProSAAS thus represents a possible therapeutic target in neurodegenerative disease.",
author = "Jarvela, {Timothy S} and Lam, {Hoa A} and Michael Helwig and Nikolai Lorenzen and Otzen, {Daniel E} and McLean, {Pamela J} and Maidment, {Nigel T} and Iris Lindberg",
year = "2016",
month = jul,
day = "25",
doi = "10.1073/pnas.1601091113",
language = "English",
volume = "113",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "The National Academy of Sciences of the United States of America",
number = "32",

}

RIS

TY - JOUR

T1 - The neural chaperone proSAAS blocks α-synuclein fibrillation and neurotoxicity

AU - Jarvela, Timothy S

AU - Lam, Hoa A

AU - Helwig, Michael

AU - Lorenzen, Nikolai

AU - Otzen, Daniel E

AU - McLean, Pamela J

AU - Maidment, Nigel T

AU - Lindberg, Iris

PY - 2016/7/25

Y1 - 2016/7/25

N2 - Emerging evidence strongly suggests that chaperone proteins are cytoprotective in neurodegenerative proteinopathies involving protein aggregation; for example, in the accumulation of aggregated α-synuclein into the Lewy bodies present in Parkinson's disease. Of the various chaperones known to be associated with neurodegenerative disease, the small secretory chaperone known as proSAAS (named after four residues in the amino terminal region) has many attractive properties. We show here that proSAAS, widely expressed in neurons throughout the brain, is associated with aggregated synuclein deposits in the substantia nigra of patients with Parkinson's disease. Recombinant proSAAS potently inhibits the fibrillation of α-synuclein in an in vitro assay; residues 158-180, containing a largely conserved element, are critical to this bioactivity. ProSAAS also exhibits a neuroprotective function; proSAAS-encoding lentivirus blocks α-synuclein-induced cytotoxicity in primary cultures of nigral dopaminergic neurons, and recombinant proSAAS blocks α-synuclein-induced cytotoxicity in SH-SY5Y cells. Four independent proteomics studies have previously identified proSAAS as a potential cerebrospinal fluid biomarker in various neurodegenerative diseases. Coupled with prior work showing that proSAAS blocks β-amyloid aggregation into fibrils, this study supports the idea that neuronal proSAAS plays an important role in proteostatic processes. ProSAAS thus represents a possible therapeutic target in neurodegenerative disease.

AB - Emerging evidence strongly suggests that chaperone proteins are cytoprotective in neurodegenerative proteinopathies involving protein aggregation; for example, in the accumulation of aggregated α-synuclein into the Lewy bodies present in Parkinson's disease. Of the various chaperones known to be associated with neurodegenerative disease, the small secretory chaperone known as proSAAS (named after four residues in the amino terminal region) has many attractive properties. We show here that proSAAS, widely expressed in neurons throughout the brain, is associated with aggregated synuclein deposits in the substantia nigra of patients with Parkinson's disease. Recombinant proSAAS potently inhibits the fibrillation of α-synuclein in an in vitro assay; residues 158-180, containing a largely conserved element, are critical to this bioactivity. ProSAAS also exhibits a neuroprotective function; proSAAS-encoding lentivirus blocks α-synuclein-induced cytotoxicity in primary cultures of nigral dopaminergic neurons, and recombinant proSAAS blocks α-synuclein-induced cytotoxicity in SH-SY5Y cells. Four independent proteomics studies have previously identified proSAAS as a potential cerebrospinal fluid biomarker in various neurodegenerative diseases. Coupled with prior work showing that proSAAS blocks β-amyloid aggregation into fibrils, this study supports the idea that neuronal proSAAS plays an important role in proteostatic processes. ProSAAS thus represents a possible therapeutic target in neurodegenerative disease.

U2 - 10.1073/pnas.1601091113

DO - 10.1073/pnas.1601091113

M3 - Journal article

C2 - 27457957

VL - 113

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 32

ER -