Description

This lecture looks at how a better understanding of the workings of the protein homoeostasis system will lead to an improved understanding of many diseases such as Alzheimer's disease, Huntington's disease, amyotrophic lateral sclerosis, cystic fibrosis or myopathies. This work may also provide potential targets for treatment of these diseases. Cells have to cope with stressful conditions and adapt to changing environments. Heat stress, heavy metal ions or UV stress induce damage to cellular proteins and disturb the balanced status of the proteome. The adjusted balance between folded and folding proteins, called protein homoeostasis, is required for every aspect of cellular functionality. Protective proteins called chaperones are expressed under extreme conditions in order to prevent aggregation of cellular proteins and safeguard protein quality. These chaperones co-operate during de novo folding, refolding and disaggregation of damaged proteins and in many cases refold them to their functional state. Even under physiological conditions these machines support protein homoeostasis and maintain the balance between de novo folding and degradation. Mutations generating unstable proteins, which are observed in numerous human diseases such as Alzheimer's disease, Huntington's disease, amyotrophic lateral sclerosis, cystic fibrosis or myopathies, also challenge the protein quality control system. A better knowledge of how the protein homoeostasis system is regulated will lead to an improved understanding of these diseases and the discovery of new targets for therapy.