How and why certain proteins misfold and how this misfolding is linked to many disease processes has become a well-documented topic of study. Protein Misfolding and Cellular Stress in Disease and Aging: Concepts and Protocols moves beyond the basics to emphasize the molecular effects of protein misfolding at a cellular level, to delineate the impacts and cellular reactions that play a role in pathogenetic mechanisms, and to pinpoint possible manipulations and treatment strategies that can counteract, modify, or delay the consequences of misfolding. The volume begins with several concepts and approaches developed in the recent past including a connection to the research field of aging, where protein misfolding diseases have been equated to premature aging processes, and the book's coverage continues with detailed descriptions of protocols for relevant experimental approaches. Written in the highly successful Methods in Molecular Biology (TM) series format, protocols chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Protein Misfolding and Cellular Stress in Disease and Aging: Concepts and Protocols aims to aid researchers in the field, as well as medical professionals and molecular biologists, in shaping and performing research related to this intriguing and vital subject.

For decades it has been known that structured conformations are important for the proper functioning of most cellular proteins. However, appreciation that protein folding to the functional conformations as well as the structural maintenance of protein molecules are very complex processes has only emerged during the last ten years. The intimate interplay uncovered by this scientific development led us to realize that perturbations of the protein folding process and disturbances of conformational maintenance are major disease mechanisms. This development has given rise to the concept of conformational diseases and the broader signature of protein folding diseases, comprising diseases in which mutations or environmental stresses may result in a partial misfolding that leads then to alternative conformations capable of disturbing cellular processes. This may happen by self-association (aggregation), as in prion and Alzheimer's diseases, or by incorporation of alternatively folded subunits into structural entities, as in collagen diseases. Another possibility is that folding to the native structure is impaired or abolished, resulting in decreased stea- state levels of the correctly folded protein, as is observed in cystic fibrosis and 1-antitrypsin deficiency, as well as in many enzyme deficiencies. In addition, deficiencies of proteins that are engaged in assisting and supervising protein folding (protein quality control) may impair the folding of many other proteins, resulting in pathological phenotypes. Examples of this are the spastic paraplegia attributable to mutations in mitochondrial protease/chaperone complexes.

For decades it has been known that structured conformations are important for the proper functioning of most cellular proteins. However, appreciation that protein folding to the functional conformations as well as the structural maintenance of protein molecules are very complex processes has only emerged during the last ten years. The intimate interplay uncovered by this scientific development led us to realize that perturbations of the protein folding process and disturbances of conformational maintenance are major disease mechanisms. This development has given rise to the concept of conformational diseases and the broader signature of protein folding diseases, comprising diseases in which mutations or environmental stresses may result in a partial misfolding that leads then to alternative conformations capable of disturbing cellular processes. This may happen by self-association (aggregation), as in prion and Alzheimer s diseases, or by incorporation of alternatively folded subunits into structural entities, as in collagen diseases. Another possibility is that folding to the native structure is impaired or abolished, resulting in decreased stea- state levels of the correctly folded protein, as is observed in cystic fibrosis and 1-antitrypsin deficiency, as well as in many enzyme deficiencies. In addition, deficiencies of proteins that are engaged in assisting and supervising protein folding (protein quality control) may impair the folding of many other proteins, resulting in pathological phenotypes. Examples of this are the spastic paraplegia attributable to mutations in mitochondrial protease/chaperone complexes."

How and why certain proteins misfold and how this misfolding is linked to many disease processes has become a well-documented topic of study. Protein Misfolding and Cellular Stress in Disease and Aging: Concepts and Protocols moves beyond the basics to emphasize the molecular effects of protein misfolding at a cellular level, to delineate the impacts and cellular reactions that play a role in pathogenetic mechanisms, and to pinpoint possible manipulations and treatment strategies that can counteract, modify, or delay the consequences of misfolding. The volume begins with several concepts and approaches developed in the recent past including a connection to the research field of aging, where protein misfolding diseases have been equated to premature aging processes, and the book's coverage continues with detailed descriptions of protocols for relevant experimental approaches. Written in the highly successful Methods in Molecular Biology (TM) series format, protocols chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Protein Misfolding and Cellular Stress in Disease and Aging: Concepts and Protocols aims to aid researchers in the field, as well as medical professionals and molecular biologists, in shaping and performing research related to this intriguing and vital subject.

In this unique overview of the Hsp60 chaperonin, Peter Bross addresses molecular biologists, medical research scientists and individuals interested in molecular or general biology. First, Bross discusses the basics of the Hsp60 chaperonin in terms of its structure and the molecular mechanisms determining its function. Second, the author highlights the multiple roles of Hsp60 for cellular systems and regulatory pathways, especially in connection with neurodegenerative diseases caused by Hsp60 deficiency. Finally, the author highlights controversial observations suggesting additional, non-standard functions of Hsp60 in and outside mitochondria as well as possible gaps in our understanding of the chaperonin. This volume serves as a snapshot suitable for experienced researcher working in fields related to molecular chaperones yet still accessible to researchers entering the field.