Book contents
- Frontmatter
- Contents
- Contributors
- Part I General Principles of Cell Death
- Part II Cell Death in Tissues and Organs
- 11 Cell Death in Nervous System Development and Neurological Disease
- 12 Role of Programmed Cell Death in Neurodegenerative Disease
- 13 Implications of Nitrosative Stress-Induced Protein Misfolding in Neurodegeneration
- 14 Mitochondrial Mechanisms of Neural Cell Death in Cerebral Ischemia
- 15 Cell Death in Spinal Cord Injury – An Evolving Taxonomy with Therapeutic Promise
- 16 Apoptosis and Homeostasis in the Eye
- 17 Cell Death in the Inner Ear
- 18 Cell Death in the Olfactory System
- 19 Contribution of Apoptosis to Physiologic Remodeling of the Endocrine Pancreas and Pathophysiology of Diabetes
- 20 Apoptosis in the Physiology and Diseases of the Respiratory Tract
- 21 Regulation of Cell Death in the Gastrointestinal Tract
- 22 Apoptosis in the Kidney
- 23 Physiologic and Pathological Cell Death in the Mammary Gland
- 24 Therapeutic Targeting Apoptosis in Female Reproductive Biology
- 25 Apoptotic Signaling in Male Germ Cells
- 26 Cell Death in the Cardiovascular System
- 27 Cell Death Regulation in Muscle
- 28 Cell Death in the Skin
- 29 Apoptosis and Cell Survival in the Immune System
- 30 Cell Death Regulation in the Hematopoietic System
- 31 Apoptotic Cell Death in Sepsis
- 32 Host–Pathogen Interactions
- Part III Cell Death in Nonmammalian Organisms
- Plate section
- References
13 - Implications of Nitrosative Stress-Induced Protein Misfolding in Neurodegeneration
from Part II - Cell Death in Tissues and Organs
Published online by Cambridge University Press: 07 September 2011
- Frontmatter
- Contents
- Contributors
- Part I General Principles of Cell Death
- Part II Cell Death in Tissues and Organs
- 11 Cell Death in Nervous System Development and Neurological Disease
- 12 Role of Programmed Cell Death in Neurodegenerative Disease
- 13 Implications of Nitrosative Stress-Induced Protein Misfolding in Neurodegeneration
- 14 Mitochondrial Mechanisms of Neural Cell Death in Cerebral Ischemia
- 15 Cell Death in Spinal Cord Injury – An Evolving Taxonomy with Therapeutic Promise
- 16 Apoptosis and Homeostasis in the Eye
- 17 Cell Death in the Inner Ear
- 18 Cell Death in the Olfactory System
- 19 Contribution of Apoptosis to Physiologic Remodeling of the Endocrine Pancreas and Pathophysiology of Diabetes
- 20 Apoptosis in the Physiology and Diseases of the Respiratory Tract
- 21 Regulation of Cell Death in the Gastrointestinal Tract
- 22 Apoptosis in the Kidney
- 23 Physiologic and Pathological Cell Death in the Mammary Gland
- 24 Therapeutic Targeting Apoptosis in Female Reproductive Biology
- 25 Apoptotic Signaling in Male Germ Cells
- 26 Cell Death in the Cardiovascular System
- 27 Cell Death Regulation in Muscle
- 28 Cell Death in the Skin
- 29 Apoptosis and Cell Survival in the Immune System
- 30 Cell Death Regulation in the Hematopoietic System
- 31 Apoptotic Cell Death in Sepsis
- 32 Host–Pathogen Interactions
- Part III Cell Death in Nonmammalian Organisms
- Plate section
- References
Summary
Summary
Several chronic neurodegenerative disorders manifest deposits of misfolded or aggregated proteins. Genetic mutations are the root cause for protein misfolding in rare families, but the majority of patients have sporadic forms possibly related to environmental factors. In some cases, the ubiquitin-proteasome system or molecular chaperones can prevent accumulation of aberrantly folded proteins. Recent studies suggest that generation of excessive nitric oxide (NO) and reactive oxygen species, in part due to overactivity of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor, can mediate protein misfolding in the absence of genetic mutation. S-Nitrosylation, or covalent reaction of NO with specific protein thiol groups, represents one mechanism contributing to NO-induced protein misfolding and neurotoxicity. Here, we present evidence suggesting that NO contributes to protein misfolding via S-nitrosylating protein-disulfide isomerase or the E3 ubiquitin ligase parkin. We discuss how the drugs memantine or NitroMemantine can inhibit excessive NMDA receptor activity to ameliorate NO production, protein misfolding, and neurodegeneration.
- Type
- Chapter
- Information
- ApoptosisPhysiology and Pathology, pp. 145 - 152Publisher: Cambridge University PressPrint publication year: 2011