- Juenemann Katrin, Jansen Anne H. P., van Riel Luigi, Merkx Remco, Mulder Monique P. C., An Heeseon, Statsyuk Alexander, Kirstein Janine, Ovaa Huib, Reits Eric A. Dynamic recruitment of ubiquitin to mutant huntingtin inclusion bodies Scientific reports 2018;8 (1):1405 [PubMed]
- Jansen Anne H. P., van Hal Maurik, Op den Kelder Ilse C., Meier Romy T., de Ruiter Anna-Aster, Schut Menno H., Smith Donna L., Grit Corien, Brouwer Nieske, Kamphuis Willem, Boddeke H. W. G. M., den Dunnen Wilfred F. A., van Roon Willeke M. C., Bates Gillian P., Hol Elly M., Reits Eric A. Frequency of nuclear mutant huntingtin inclusion formation in neurons and glia is cell-type-specific Glia 2017;65 (1):50-61 [PubMed]
- Wiemhoefer Anne, Stargardt Anita, van der Linden Wouter A., Renner Maria C., van Kesteren Ronald E., Stap Jan, Raspe Marcel A., Tomkinson Birgitta, Kessels Helmut W., Ovaa Huib, Overkleeft Herman S., Florea Bogdan, Reits Eric A. Tripeptidyl Peptidase II Mediates Levels of Nuclear Phosphorylated ERK1 and ERK2 Molecular & cellular proteomics 2015;14 (8):2177-2193 [PubMed]
- Schipper-Krom Sabine, Juenemann Katrin, Jansen Anne H., Wiemhoefer Anne, van den Nieuwendijk Rianne, Smith Donna L., Hink Mark A., Bates Gillian P., Overkleeft Hermen, Ovaa Huib, Reits Eric Dynamic recruitment of active proteasomes into polyglutamine initiated inclusion bodies FEBS letters 2014;588 (1):151-159 [PubMed]
- Juenemann Katrin, Schipper-Krom Sabine, Wiemhoefer Anne, Kloss Alexander, Sanz Sanz Alicia, Reits Eric A. J. Expanded Polyglutamine-containing N-terminal Huntingtin Fragments Are Entirely Degraded by Mammalian Proteasomes Journal of biological chemistry 2013;288 (38):27068-27084 [PubMed]
2008 NWO VIDI personal grant to study and improve the clearance of polyQ fragments and aggregates
2004 NWO VENI personal research grant to study protein and peptide clearance
2000 Antonie van Leeuwenhoekprijs (award of the Netherlands Cancer Institute for a high-potential researcher)
Doctorate University: University Leiden, cum laude 25-10-2001
Supervisor: Prof. Dr. Jacques J. Neefjes
Title of thesis: Dynamics of Antigen Processing in Living Cells
Prof. PhD E.A.J. Reits (IMPROVING PROTEIN DEGRADATION IN HUNTINGTON’S DISEASE)
Huntington’s Disease (HD) is an dominant inherited neurodegenerative disorder with the combined symptoms of Alzheimer, Parkinson and ALS. HD is caused by a mutation in the gene encoding the huntington protein. Due to the expansion of the CAG repeat in the gene the encoded huntington protein had an extended repeat of glutamine amino acids (polyQ) in the protein. Due to the repeat expansion the mutant Htt protein (mHtt) aggregates in neuronal cells, leading to their dysfunction, with consequences for memory and movement and psychiatric problems. Following the first symptoms the patient will live on average 15-17 years.
Improving the degradation of these mHtt fragments prior to aggregation would be a therapeutic strategy for this devastating disease for which there is no cure.
The main protein degradation machinery in cells is the Ubiquitin-Proteasome System (UPS) which is present in both the cytoplasm and nucleus. It degrades both short-lived, misfolded proteins and long-lived proteins that are mainly targeted for degradation via ubiquitination. The role of the UPS in HD is however controversial since UPS impairment has been observed in various HD models, which could be due to sequestration of proteasomes into aggregates (inclusion bodies, IB) that are initiated by mHTT. In addition, proteasomes may even be unable to cleave within the polyglutamine (polyQ) expansion in mHTT that is caused by the CAG repeat expansion in the mutated gene. Proteasomes may become clogged by these fragments or release polyQ peptides when polyQ-expanded proteins are inefficiently degraded.
Our research group have addressed various research questions with relation to the UPS and its role in the degradation of mHtt.
PhD N.N. van der Wel
PhD A.E. Bury
PhD S. Krom
PhD K.A. Sap
PhD M. Tohti
MSc J. Janzen
A. Sanz Sanz
- Birmingham Women's Hospital
- CHDI Foundation, Inc., c/o CHDI Management, Inc.
- KWF Kankerbestrijding
- Stichting AMC Foundation (Vrijgesteld)
- Stichting Immuno Valley
- Stichting Zeldzame Ziekten Fonds