Handling Editor: Giampietro Schiavo
ABSTRACT
Protein aggregates that result in inclusion formation are a pathological hallmark common to many neurodegenerative diseases, including amyotrophic lateral sclerosis, Parkinson's disease and Huntington's disease. Under conditions of cellular stress, activation of the heat shock response (HSR) results in an increase in the levels of molecular chaperones and is a first line of cellular defence against inclusion formation. It remains to be established whether neurodegenerative disease-associated proteins and inclusions are themselves capable of inducing an HSR in neuronal cells. To address this, we generated a neuroblastoma cell line that expresses a fluorescent reporter protein under conditions of heat shock transcription factor 1 (HSF1)-mediated HSR induction. We show that the HSR is not induced by exogenous treatment with aggregated forms of recombinant α-synuclein or the G93A mutant of superoxide dismutase-1 (SOD1G93A) nor intracellular expression of SOD1G93A or a pathogenic form of polyglutamine-expanded huntingtin (Htt72Q). These results suggest that pathogenic proteins evade detection or impair induction of the HSR in neuronal cells. A failure of protein aggregation to induce an HSR might contribute to the development of inclusion pathology in neurodegenerative diseases.
This article has an associated First Person interview with the first author of the paper.
Footnotes
Competing interests
The authors declare no competing or financial interests.
Author contributions
Conceptualization: R.S.G., J.J.Y., L.O., H.E.; Methodology: R.S.G., D.C., L.M., T.B., J.J.Y., L.O., H.E.; Software: R.S.G.; Validation: R.S.G., T.B., H.E.; Formal analysis: R.S.G., D.C., T.B.; Investigation: R.S.G., D.C., L.M., T.B., A.K.W., J.J.Y., L.O., H.E.; Resources: R.S.G., H.E.; Data curation: R.S.G.; Writing - original draft: R.S.G., H.E.; Writing - review & editing: R.S.G., D.C., L.M., T.B., A.K.W., J.J.Y., L.O., H.E.; Visualization: R.S.G., D.C., A.K.W., J.J.Y., L.O., H.E.; Supervision: T.B., J.J.Y., L.O., H.E.; Project administration: T.B., J.J.Y., L.O., H.E.; Funding acquisition: J.J.Y., L.O., H.E.
Funding
R.S.G. was supported with an Australian Government Research Training Program Scholarship whilst she undertook this work and is currently supported by a FightMND Early Career Fellowship. L.M. is supported by the Bill Gole Postdoctoral Fellowship (MNDRA, Motor Neurone Disease Australia). J.J.Y. is supported by a University of Wollongong Professorship in neurodegenerative diseases. A.K.W. is funded by the Australian National Health and Medical Research Council (R.D. Wright Career Development Fellowship GNT1140386 to A.K.W.), the Ross Maclean Fellowship (University of Queensland), and the Brazil Family Program for Neurology.
Supplementary information
Supplementary information available online at https://jcs.biologists.org/lookup/doi/10.1242/jcs.243709.supplemental
- Received May 12, 2020.
- Accepted June 30, 2020.
- © 2020. Published by The Company of Biologists Ltd
Log in using your username and password
Log in through your institution
Pay Per Article - You may access this article (from the computer you are currently using) for 1 day for US$30.00 .
Regain Access - You can regain access to a recent Pay per Article purchase if your access period has not yet expired.
Article navigation
Related articles
Cited by...
More in this TOC section
Similar articles
Subject collections
Other journals from The Company of Biologists
2020 at The Company of Biologists
Despite the challenges of 2020, we were able to bring a number of long-term projects and new ventures to fruition. While we look forward to a new year, join us as we reflect on the triumphs of the last 12 months.
Mole – The Corona Files
"This is not going to go away, 'like a miracle.' We have to do magic. And I know we can."
Mole continues to offer his wise words to researchers on how to manage during the COVID-19 pandemic.
Cell scientist to watch – Christine Faulkner
In an interview, Christine Faulkner talks about where her interest in plant science began, how she found the transition between Australia and the UK, and shares her thoughts on virtual conferences.
Read & Publish participation extends worldwide
“The clear advantages are rapid and efficient exposure and easy access to my article around the world. I believe it is great to have this publishing option in fast-growing fields in biomedical research.”
Dr Jaceques Behmoaras (Imperial College London) shares his experience of publishing Open Access as part of our growing Read & Publish initiative. We now have over 60 institutions in 12 countries taking part – find out more and view our full list of participating institutions.
JCS and COVID-19
For more information on measures Journal of Cell Science is taking to support the community during the COVID-19 pandemic, please see here.
If you have any questions or concerns, please do not hestiate to contact the Editorial Office.