title: High pressure, an alternative approach to understand protein misfolding diseases.
abstract: Protein folding is essential for the flow of genetic information to biological activity. A failure in this process can result in disease, by causing cell damage and sometimes death. The misfolding of proteins often induces their aggregation, initiating the fibril formation seen in a range of human and animal diseases. Because misfolding and aggregation are of fundamental importance in vivo, there is currently great interest in understanding their mechanisms. To gain insight into the folding and unfolding processes of proteins, for nearly a century, an original biophysical approach has been successfully used: the application of high hydrostatic pressure combined with various spectroscopic and kinetic techniques. Because high pressure provides new insight into protein structure and folding which cannot be obtained by other techniques, the conformations of pressure-induced unfolding intermediates and species involved in the initial states of aggregation of proteins associated with specific diseases are currently being investigated. Our contention is that by exploring folding kinetics, misfolding pathways and stability under pressure, it will be possible to understand the mechanisms of amyloidogenesis, with the ultimate goal to design therapeutic strategies to prevent progression of the disease.
authors.affiliation: EA 3763, INSERM U432, CC 105, Université Montpellier, Montpellier, France.
authors.forename: J
authors.initials: J
authors.lastname: Torrent
authors.forename: S
authors.initials: S
authors.lastname: Marchal
authors.forename: P
authors.initials: P
authors.lastname: Tortora
authors.forename: R
authors.initials: R
authors.lastname: Lange
authors.forename: C
authors.initials: C
authors.lastname: Balny
mesh_terms: D000682:Amyloid / Q000737:chemistry / Q000502:physiology; D000818:Animals; D000067699:Ataxin-3; D004194:Disease / Q000209:etiology; D006801:Humans; D008722:Methods; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000502:physiology; D009687:Nuclear Proteins; D011312:Pressure; D011328:Prions / Q000737:chemistry / Q000502:physiology; D011489:Protein Denaturation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry* / Q000502:physiology; D012097:Repressor Proteins
chemical_list: D000682:Amyloid; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D011328:Prions; D011506:Proteins; D012097:Repressor Proteins; C092341:ATXN3 protein, human; D000067699:Ataxin-3