In the last 50 years a wealth of information has allowed us to understand the contribution of various regulatory factors that alter mRNA and protein s- thesis to a variety of physiological and pathological conditions. However, such regulation is only one of many factors that contribute to the levels of a given p- tein. One major factor that has been relatively obscure until recently has been the contribution of protein degradation to the regulation of the steady state level of protein expression and protein function. This rapidly evolving field has made a significant mark on the scientific community, as highlighted by the Award of the Nobel Prize in Chemistry for 2004 to Aaron Ciechanover, Avram Hershko and Irwin Rose for their pioneering work on the ubiquitin-proteasome system (UPS) of protein degradation, which is the subject of this volume. In recent years e- dence has been accumulating that suggests a role for UPS function in both ph- iological and pathological settings. In particular, studies have implicated a central role for the UPS in cell cycle regulation, cancer and neurodegeneration. Two points are however worth bearing in mind: First, ubiquitin's function appears to extend far beyond the UPS and protein degradation; second, there are other important systems of intracellular protein degradation, most notably autophagic systems through the lysosomes, and these may also be involved in disease pat- physiology.

Addresses the increasingly important theme of proteasomes Includes supplementary material: sn.pub/extras

Klappentext

"Protein degradation, especially via the ubiquitin-proteosome system, has emerged as a critical molecular component to mechanisms of cell death in a variety of prominent neurodegenerative diseases. Thus, the editors of this book should be praised for the comprehensiveness and timeliness of their effort. In this single volume, the reader will find a mixture of valuable information regarding the ubiquitin-proteosome machinery ranging from the most basic to the most clinically-relevant. The book also provides insightful comments and views on the complex question of ubiquitin-proteosome
in neurodegeneration by well-respected experts, which enrich this volume with many balanced opinionsand a scientific honesty rarely found in these types of books. It is unquestionable that this publication would be an asset to any neuroscientist and clinician alike."

Serge Przedborski, Columbia University

Impaired function of the ubiquitin-proteosome system (UPS) has long been implicated as a contributing factor in various neurodegenerative diseases. In fact, the presence of various ubiquitin-decorated protein aggregates is pathonumonic for many such diseases. Unfortunately, this system was sorely neglected until the recent association between several genes, encoding UPS-related proteins, and Parkinson's disease placed UPS dysfunction center stage in the neurodegeneration field. With increasing interest in this fast growing area, this book represents a timely and critical effort summarizing the most exciting development to date by many renown experts in the field. With a thoughtful and useful structure, the book takes the reader from a detailed introduction of the UPS system, through an elegant discussion of the relationship between UPS and critical cellular functions to an outstanding summary of the UPS in various neurodegenerative diseases. As such, this book serves equally well to both those who are new and those who are knowledgeable to the field. There is nodoubt that this book will generate ever more interest in this fertile research area.

Mark A. Smith, Case Western Reserve University

This is excellent timing! The role of the ubiquitin proteasome system in neurodegeneration is a hot topic, and recent research has shown that this system plays a role in various neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease and Huntington's disease.

This book contains up-to-date reviews on different aspects of the ubiquitin proteasome system and its involvement in several neurodegenerative diseases. It is an indispensable source of information for scientists studying neurodegeneration. The book provides information on the basics of the ubiquitin proteasome system, but mainly describes a number of aspects of involvement of this system in neurodegeneration. All major hypotheses on the possible causes of neurodegeneration, such as oxidative stress, inflammation, and aging, are discussed in view of their effect on the ubiquitin proteasome system.

The contributions and different views from leading authors in the field provide a balanced, comprehensive and up-to-date view of the possible role of the proteasome in neurodegeneration. The book is a unique reference work for all biological and medical researchers working in the field of neurodegeneration.

Elly M. Hol, Cellular Quality Control Netherlands Institute for Brain Research

Inhalt
Basic Aspects of Protein Degradation Through the Ubiquitin Proteasome System (UPS).- Yeast Proteasome Structure and Biogenesis.- Ubiquitin-Proteasome System in the Central Nervous System.- Protein Aggregation, Inclusion Formation and Ups Function.- Protein Aggregation and the UPS: A Two-Way Street.- The Impact of Inclusion Formation on Cell Survival.- Inclusion Formation and Disolution Following Proteasomal Inhibition in Neuronal Cells.- Oxidative Stress and Ups Function.- The Proteasome: Source and a Target of Oxidative Stress?.- Inflammation as a Mediator of Oxidative Stress and UPS Dysfunction.- Proteasome and Neuronal Cell Death and Survival.- Role of the Ubiquitin Proteasome System During Neuronal Cell Death.- Pathways of Neuronal Cell Death Induced by Proteasomal Inhibition.- Models of Dysfunction of the UPS and the Proteasome.- Pharmacological and Molecular Models of Proteasomal Dysfunction.- The Gad Mouse: A Window Into UPS-Related Neurodegeneration and the Function of the Function of the Deubiquitinating Enzyme Uch-L1.- The UPS in Neurodegenerative Diseases and Aging.- Parkinson's Disease and Related Disorders.- Ubiquitination by Parkin Implications in Parkinson's Disease.- The Ups in Neurodegenerative Diseases and Aging Huntington's Disease.- Frameshift Mutant Ubiquitin in Alzheimer's Disease and Other Neurodegenerative Disorders.- Motor Neuron Disease.- The Paradoxical Role of Proteasomes in Prion Disorders.- Aging and the Proteasome.