Journal of Biological Chemistry
Molecular Bases of DiseaseDisassembly of Tau fibrils by the human Hsp70 disaggregation machinery generates small seeding-competent species
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Author contributions—E. N., T. R. J., B. B., and C. N.-K. conceptualization; E. N., A. S. W., K. M., L. B., T. K., K. A., W. A. M., R. M., and C. N.-K. resources; E. N. formal analysis; E. N., L. B., W. A. M., T. R. J., R. M., B. B., and C. N.-K. supervision; E. N., A. S. W., H. K., T. R. J., R. M., B. B., and C. N.-K. funding acquisition; E. N. validation; E. N. investigation; E. N. and C. N.-K. visualization; E. N., A. S. W., K. M., L. B., T. K., W. A. M., R. M., and A. M. methodology; E. N. and C. N.-K. writing-original draft; E. N. and C. N.-K. project administration; E. N., A. S. W., T. K., H. K., W. A. M., T. R. J., R. M., A. M., B. B., and C. N.-K. writing-review and editing.
Funding and additional information—This study is part of the PROTEST-70 project within the EU Joint Programme–Neurodegenerative Disease Research (JPND) project. This project is supported through the following funding organizations under the aegis of JPND: France, Agence National de la Recherche (ANR, ANR-17-JPCD-0005-01 to R. M.); Germany, Bundesministerium für Bildung und Forschung (BMBF; 01ED1807A to B. B. and 01ED1807B to C. N.-K.); The Netherlands, Netherlands Organization for Scientific Research (ZonMw; project number 733051076). Funding was also provided by Alzheimer Forschung Initiative e.V. (AFI), grant 17054 (to B. B.), the Baden-Württemberg Stiftung, BWST-ISFIII-029 (to A. S. W. and B. B.), Centre National de la Recherche Scientifique, the Institut de France-Fondation Simone et Cino Del Duca, and the Fondation pour la Recherche Médicale (contract DEQ 20160334896). Cambridge Brain Bank is part of the Human Research Tissue Bank and is supported by the NIHR Cambridge Biomedical Research Centre. This work was supported by the UK Dementia Research Institute, which receives its funding from DRI Ltd., funded by the UK Medical Research Council, Alzheimer’s Society and Alzheimer’s Research UK. This work has also received support from the EU/EFPIA/Innovative Medicines Initiative 2 Joint Undertaking (IMPRiND grant no. 116060). W. A. M. was supported by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (grant number 206248/Z/17/Z). E. N. was supported by Ph.D. fellowships from the Helmholtz International Graduate School for Cancer Research (DKFZ), the Chica and Heinz Schaller Foundation, and the Studienstiftung des deutschen Volkes.
Conflict of interest—No author has an actual or perceived conflict of interest with the contents of this article.
Present address for Thomas R. Jahn: AbbVie Deutschland GmbH & Co. KG, Ludwigshafen, Germany
Abbreviations—The abbreviations used are:
- AD
Alzheimer's disease
- HD
Huntington's disease
- Hsp
heat shock protein
- HSPA4
heat shock protein family A (Hsp70) member 4 (APG2)
- HSPA8
heat shock protein family A (Hsp70) member 8 (HSC70)
- NEF
nucleotide exchange factor
- PD
Parkinson's disease
- TEM
transmission electron microscopy
- ThT
thioflavin T
- ANOVA
analysis of variance.