Protein folding, misfolding and aggregation, as well as the way misfolded and aggregated proteins affects cell viability are emerging as key themes in molecular and structural biology and in molecular medicine. Recent advances in the knowledge of the biophysical basis of protein folding have led to propose the energy landscape theory which provides a consistent framework to better understand ho...

Protein misfolding is the primary cause of several systemic and neurodegenerative diseases and a major challenge in the development of protein-based therapeutics, Figure 1 top. In misfolding diseases such as cystic fibrosis and a1-antitrypsin deficiency, degradation and/or mistrafficking of specific proteins causes loss of protein function. A second class of misfolding disease includes systemic...

This special issue includes fifteen reviews and two original research articles by leading scientists in the fields of neu-ropathology, biochemistry, and cell biology, dealing with the role of protein aggregation and prion-like propagation of protein misfolding in neurodegenerative diseases. In the review article " Breaking the code of amyloid-í µí»½ oli-gomers, " available at the following link...

The capacity of the cell to produce, fold and degrade proteins relies on components of the proteostasis network. Multiple types of insults can impose a burden on this network, causing protein misfolding. Using thermal stress, a classic example of acute proteostatic stress, we demonstrate that ∼5-10% of the soluble cytosolic and nuclear proteome in human HEK293 cells is vulnerable to misfolding ...