© 2011 • 349 pp., illus. (17 4C and 7 B&W images), index
Hardcover • £85.00 • ISBN  978-1-936113-06-4

Proper expression, folding, transport, and clearance of proteins is critical for cell function. Chaperones and enzymes that posttranslationally assist newly synthesized proteins help ensure that they fold correctly or are degraded. Translocation machineries, proteasomes, and autophagic activities help to localize and degrade proteins as necessary. Stress and aging can cause such mechanisms to become dysfunctional or overloaded, resulting in the accumulation and aggregation of misfolded proteins a feature of numerous neurodegenerative conditions.

Written and edited by experts in the field, this volume covers the entire spectrum of protein homeostasis in healthy cells and the diseases that result when control of protein production, protein folding, and protein degradation goes awry. The contributors examine the physical biochemistry of protein folding and the roles of the various cellular compartments in protein quality control, as well as approaches for ameliorating protein misfolding and aggregation diseases.

Including discussions of specific disorders such as Alzheimer’s disease, Huntington’s disease, and prion diseases, this book is an essential reference for not only molecular and cellular biologists but also medical scientists wishing to understand the pathological consequences of and potential therapies for protein homeostasis deficiencies in common human diseases.

I. Chemistry and Biology of Proteostasis

Physical Biochemistry of Protein Folding and Misfolding

Michele Vendruscolo, Tuomas P. J. Knowles, and Christopher M. Dobson

Integrating Protein Homeostasis Strategies in Prokaryotes

Axel Mogk, Damon Huber, and Bernd Bukau

Cellular Strategies of Protein Quality Control

Bryan Chen, Marco Retzlaff, Thomas Roos, and Judith Frydman

Integration of Clearance Mechanisms: The Proteasome and Autophagy

Esther Wong and Ana Maria Cuervo

Aging as an Event of Proteostasis Decline

Rebecca C. Taylor and Andrew Dillin

The Stress of Protein Misfolding: From Single Cells to Multicellular Organisms

Tali Gidalevitz, Veena Prahlad, and Richard I. Morimoto

 

II. Protein Quality Control in Cellular Compartments

Protein Folding in the Cytoplasm and the Heat Shock Response

Martin Vabulas, Swasti Raychaudhuri, Manajit Hayer-Hartl, and F. Ulrich Hartl

Protein folding and quality control in the ER

Kazutaka Araki and Kazuhiro Nagata

Stress and its Functional Link to Mitochondria: Role in Cell Survival and Death

Jyoti D. Malhotra and Randy Kaufman

Quality Control of Mitochondrial Proteostasis

Michael J. Baker, Takashi Tatsuta, and Thomas Langer

 

III. Disorders of Protein Homeostasis

Hepatic Fibrosis and Carcinogenesis in Alpha-1-Antitrypsin Deficiency: A Prototype For Chronic Tissue Damage in Gain-of-Function Disorders

David H. Perlmutter and Gary A. Silverman

Alzheimer Disease

Dennis J. Selkoe

Huntingtons’ Disease

Steven Finkbeiner

Proteostasis and Movement Disorders: Parkinson’s Disease and Amyotrophic Lateral Sclerosis

Daryl A. Bosco, Matthew J. LaVoie, Gregory A. Petsko, and Dagmar Ringe

Prions

David W. Colby and Stanley B. Prusiner

Emergent Properties of Proteostasis in Managing Cystic Fibrosis

William E. Balch, Daniela Roth, and Darren M. Hutt

Protein Misfolding and Retinal Degeneration

Radouil Tzekov, Linda Stein, and Shalesh Kaushal

Chemical and Biological Approaches for Adapting Proteostasis to Ameliorate Protein Misfolding and Aggregation Diseases–Progress and Prognosis

Susan L. Lindquist and Jeffery W. Kelly

 

Index