Tsaytler, P., Harding, H. P., Ron, D., and Bertolotti, A. (2011)
Selective Inhibition of a Regulatory Subunit of Protein Phosphatase 1 Restores Proteostasis.
Science 332, 91-94.
Comment in Science. 2011 Apr 1;332(6025):44-5.
Munch, C., O'Brien, J., and Bertolotti, A. (2011).
Prion-like propagation of mutant superoxide dismutase-1 misfolding in neuronal cells.
Proc Natl Acad Sci USA, 108, 3548-3553.
Munch, C., and Bertolotti, A. (2010).
Exposure of hydrophobic surfaces initiates aggregation of diverse ALS-causing superoxide dismutase-1 mutants.
J Mol Biol 399, 512-525.
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Group Members
- Christian Munch
- Pavel Tsaytler
- Ariane Hanssum
- Zhen Zhong
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Deposition of proteins of aberrant conformation is the hallmark of several neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis and prion disorders. Cells have elaborated quality control mechanisms to protect them from the deleterious effect of misfolded proteins.
The two main effectors of quality control pathways are molecular chaperones, which refold abnormally folded polypeptides or direct them to degradation machinery, and the degradation machinery itself. Yet, quality control may not always be perfectly efficient and failure to refold or to degrade aberrant proteins leads to their accumulation and subsequent aggregation.
Accumulation of misfolded proteins represents a threat for proper cell function. Neurons, as post-mitotic cells, are thought to be particularly sensitive to misfolding injury because they lack the possibility to dilute their proteotoxins through cell division. Furthermore, accumulation of aberrant proteins increases with age, when quality control becomes less efficient.
Neurodegenerative diseases characterized by accumulation of misfolded proteins have late onset, implying that the proteins
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responsible for these diseases cause cellular dysfunction specifically in aged neurons while being benign for many years.
Using various complementary approaches, our aim is to characterize the events triggering protein aggregation. Our work might contribute to a better comprehension of the molecular mechanisms allowing the cells to cope with the burden of misfolded proteins. In addition, it may open the way to a better understanding of the ageing process.
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Group Leaders 
