The Proteasome in Neurodegeneration

1. Front Matter

   Pages i-xv

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2. Basic Aspects of Protein Degradation Through the Ubiquitin Proteasome System (UPS)

   1. Yeast Proteasome Structure and Biogenesis

      • Cordula Enenkel

      Pages 1-16

   2. Ubiquitin-Proteasome System in the Central Nervous System

      • Qunxing Ding, Jeffrey N. Keller

      Pages 17-37

3. Protein Aggregation, Inclusion Formation and Ups Function

   1. Protein Aggregation and the UPS: A Two-Way Street

      • Kostas Vekrellis, Leonidas Stefanis

      Pages 39-55

   2. The Impact of Inclusion Formation on Cell Survival

      • M. Maral Mouradian, Mikiei Tanaka, Gwang Lee, Eunsung Junn

      Pages 57-67

   3. Inclusion Formation and Disolution Following Proteasomal Inhibition in Neuronal Cells

      • Leonidas Stefanis, Hardy J. Rideout

      Pages 69-84

4. Oxidative Stress and Ups Function

   1. The Proteasome: Source and a Target of Oxidative Stress?

      • Barry Halliwell

      Pages 85-103

   2. Inflammation as a Mediator of Oxidative Stress and UPS Dysfunction

      • Thomas Schmidt-Glenewinkel, Maria Figueiredo-Pereira

      Pages 105-131

5. Proteasome and Neuronal Cell Death and Survival

   1. Role of the Ubiquitin Proteasome System During Neuronal Cell Death

      • Nadia Canu, Pietro Calissano

      Pages 133-148

   2. Pathways of Neuronal Cell Death Induced by Proteasomal Inhibition

      • Isabelle Lang-Rollin, Leonidas Stefanis

      Pages 149-165

6. Models of Dysfunction of the UPS and the Proteasome

   1. Pharmacological and Molecular Models of Proteasomal Dysfunction

      • Thomas Schmidt-Glenewinkel, Maria Figuierdo-Pereira

      Pages 167-183

   2. The Gad Mouse: A Window Into UPS-Related Neurodegeneration and the Function of the Function of the Deubiquitinating Enzyme Uch-L1

      • Jungkee Kwon, Keiji Wada

      Pages 185-198

7. The UPS in Neurodegenerative Diseases and Aging

   1. Parkinson’s Disease and Related Disorders

      • Mark Cookson

      Pages 199-212

   2. Ubiquitination by Parkin — Implications in Parkinson’s Disease

      • Sathya Ravichandran, Ted M. Dawson, Valina L. Dawson

      Pages 213-224

   3. The Ups in Neurodegenerative Diseases and Aging Huntington’s Disease

      • M. Diaz-Hernandez, J. J. Lucas

      Pages 225-235

   4. Frameshift Mutant Ubiquitin in Alzheimer’s Disease and Other Neurodegenerative Disorders

      • Robert Layfield

      Pages 237-246

   5. Motor Neuron Disease

      • Heather D. Durham, Edor Kabashi, David M. Taylor, Jeffrey N. Agar

      Pages 247-264

   6. The Paradoxical Role of Proteasomes in Prion Disorders

      • Neena Singh, Yaping Gu, Sharmila Bose, Subhabrata Basu, Xiu Luo, Ajitesh Ojha et al.

      Pages 265-283

   7. Aging and the Proteasome

      • Qunxing Ding, Jeffrey N. Keller

      Pages 285-298

8. Back Matter

   Pages 299-306

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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.

• Keller
• Nervous System
• Neurodegeneration
• Neuroscience
• Parkinson
• Proteasome
• Stefanis

• Institute of Biomedical Research of the Academy of Athens, Athens, Greece

  Leonidas Stefanis

• Sanders-Brown Center on Aging Department of Anatomy and Neurobiology, University of Kentucky, USA

  Jeffrey N. Keller

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