Expanding knowledge on protein misfolding: unravelling the molecular basis of neurodegeneration

CHEHÍN ROSANA.

Current Protein and Peptide Science

Lugar: Amsterdam; Año: 2011 p. 123

978-1-873671-00-9

Since the pioneering work of Anfinsen in 1973, the protein folding was matter of many biophysical studies. However, at the present, the protein folding studies shows a kind of renaissance with an unprecedented number of jobs in the literature driven principally by the fact that the protein aggregation in the last decade was considered as the main cause of several human diseases. In fact, protein aggregates as intracellular inclusion or intracellular deposition have been associated with various, often highly weakening diseases like Alzheimer, Parkinson, Hungtiton, for which no sufficient cure is available yet. In this scenario, scientist from different areas have converged on protein folding and the traditional knowledge undergone profound changes of paradigms. The classical energy landscape funnel that could explain the folding pathways for years was unable to explain the protein aggregation and is now replaced by a double funnel energy landscape for protein folding and aggregation proposed by Rdford and Jahn in 2005. This new concept can explain how a native protein which is structure and thermodynamically stable can reach other conformations with lower free energy state than the native state. In this point, the external variable which are able disturb the natural folding equilibrium like pH, temperature, presence of surface or small molecules acquire relevance. Protein misfolding and aggregation studies have produced a unique space in which of researchers from biochemist and biophysics biomedical and pharmacologist can interact efficiently. However, the language of one area is sometimes difficult to be completely understood by the other. But now, this interdisciplinary complementation is essential to obtain the enough amount of knowledge necessary to control the protein aggregation process. In this sense, the contribution of knowledge from different areas of science is essential. At the present, a lot of information exploiting spectroscopic and computing simulation techniques are available giving information on the aggregation pathway of proteins or peptides related with pathologies i.e. alpha-synuclein, Aβ-peptide, transthyretin or insulin. In this way, this CPPS issue is devoted to discuss the contribution of classical as well as novel biophysical techniques to define the state of the art of the molecular mechanism of protein aggregation providing useful tools to researchers from other fields to analyze the current knowledge. Moreover, the influence of new actors involved in altering the protein folding equilibrium likes membranes, glycosaminoglycans in two of the most common plegophaties are also considered.