Editorial [Hot Topic: Expanding Knowledge on Protein Misfolding: Unravelling the Molecular Basis of Neurodegeneration (Guest Editor: Rosana Chehin)]

Since the pioneering work of Anfinsen in 1973, protein folding was subject to many biophysical studies. However, the protein folding studies show a kind of renaissance nowadays. Since protein aggregation is considered as the main cause of several human diseases, an unprecedented number of scientific reports have been published in the last decade on protein aggregation. In fact, protein aggregates as intracellular inclusion or extracellular deposition have been associated with highly prevalent diseases such as Alzheimer's and Parkinson's disease, for which no cure is available yet. In this scenario, scientists from different areas have converged on protein folding and the old paradigms underwent profound changes. The classical energy landscape funnel that explained the folding pathways for years is unable to explain protein aggregation process and is now replaced by a double funnel energy landscape as proposed by Jahn and Radford in 2005. This new concept helps to understand how a native protein that is structural and thermodynamically stable can reach other conformations with even lower free energy than the native state. At this point, the external variables which may disturb the natural folding equilibrium such as pH, temperature, presence of surface or small molecules acquire relevance. Protein misfolding and aggregation studies have produced a unique space in which researchers from biochemistry and biophysics to biomedicine and pharmacology can efficiently interact. This interdisciplinary complementation is essential in order to obtain enough amount of knowledge necessary to completely understand the protein aggregation process. Of course, the language of one area might sometimes be difficult to be fully understood by the others. This is the challenge we have to deal with. But in the end, it will be extremely positive because the contributions from the different areas of science will be essential. Currently, a lot of information exploiting spectroscopic and computing simulation techniques is available giving information on the aggregation pathways of pathologies-related proteins or peptides. In this way, this CPPS issue is devoted to discuss the contributions of classical as well as novel biophysical techniques, defining the state of the art of the molecular mechanisms of protein aggregation. Hopefully it will provide useful tools to researchers from other fields for analysing the current state of knowledge. Moreover, the influence of new actors involved in altering the protein folding equilibrium such as membranes and glycosaminoglycans, are also considered.