Mitochondrial Function and Dysfunction 1st Edition by Shapira 9780080489070 0080489079

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ISBN 10: 0080489079
ISBN 13: 9780080489070 
Author:  A. Shapira

Mitochondria are critical to the survival of cells, therefore, it is not surprising that abnormalities in mitochondrial function may lead to human disease. This book concentrates on the biology and pathology of mitochondria, covering some ot the important basic science features of the biology of mitochondria. It then moves on to discuss the breadth of human diseases related to mitochondrial dysfunction, including Parkinson’s disease, Amyotrophic Lateral Sclerosis (ALS), and Alzheimer’s disease.

* Provides comprehensive coverage of basic science and clinical features of mitochondrial dysfunction
* Presents detailed analysis of “hot” topics in mitochondrial function and neurodegenerative diseases
* Includes outstanding list of contributing authors

Mitochondrial Function and Dysfunction 1st Table of contents:

SECTION I: MITOCHONDRIAL STRUCTURE AND FUNCTION
Chapter 1. Mitochondrial DNA Structure and Function
I. Mammalian Mitochondrial Genomes
II. The Human mtDNA
III. Structure of the Human mtDNA D-Loop Region
IV. Mitochondrial DNA Replication
V. Initiation of L-Strand DNA Replication
VI. Alternative Mode of mtDNA Replication
VII. General Features of Factors Associated with mtDNA Replication
VIII. Regulation of mtDNA Replication
IX. Mitochondrial Transcription
X. Translation of Mitochondrial Transcripts
XI. Concluding Remarks
References

Chapter 2. Oxidative Phosphorylation: Structure, Function, and Intermediary Metabolism
I. Historical Background
II. The Mitochondrial Electron Transport Chain
III. Intermediary Metabolism
IV. Concluding Remarks
References

Chapter 3. Import of Mitochondrial Proteins
I. Introduction
II. The Pathways of Mitochondrial Preprotein Import
III. Mitochondrial Biogenesis and Human Neurodegenerative Diseases
References

SECTION II: PRIMARY RESPIRATORY CHAIN DISORDERS
Chapter 4. Mitochondrial Disorders of the Nervous System: Clinical, Biochemical, and Molecular Genetic
I. Introduction
II. Historical Considerations
III. Genetics and Pedigree Studies
IV. Clinical Features
V. Important Clinical Questions
VI. Major Mitochondrial Syndromes
VII. Biochemical Features
VIII. Diagnostic Approaches
IX. Treatment of Mitochondrial Disorders
References

SECTION III: SECONDARY RESPIRATORY CHAIN DISORDERS
Chapter 5. Friedreich’s Ataxia
I. Features of Friedreich’s Ataxia
II. Effect of FRDA Gene Mutations
III. Models of FRDA
IV. FRDA Molecular Mechanisms
V. Therapeutic Intervention
VI. Conclusion
References

Chapter 6. Wilson Disease
I. The Role and Transport of Copper in Health
II. Aceruloplasminemia and Menkes’ Disease
III. Experimental Models of Wilson Disease
IV. Mitochondrial Dysfunction in Animal Models
V. Mitochondrial Dysfunction in Human Disease
VI. Molecular Basis for the Variation in Phenotype
VII. Diagnosis
VIII. Cranial Magnetic Resonance Imaging (MRI) and Spectroscopy in Wilson Disease
IX. Treatment
X. Conclusion
References

Chapter 7. Hereditary Spastic Paraplegia
I. Introduction
II. Clinical Features
III. Genetics
References

Chapter 8. Cytochrome c Oxidase Deficiency
I. Cytochrome c Oxidase Biogenesis
II. Nuclear Genes Affecting COX Assembly and Stability
III. Nuclear Genes Affecting mtDNA Level and/or Stability
IV. mtDNA Defects
References

SECTION IV: TOXIN-INDUCED MITOCHONDRIAL DYSFUNCTION
Chapter 9. Toxin-Induced Mitochondrial Dysfunction
I. Introduction
II. Inhibitors of Mitochondrial Complex I: NADH Ubiquinine Oxidoreductase
III. Inhibitors of Mitochondrial Complex II: Succinate Ubiquinol Oxidoreductase
IV. Inhibitors of Mitochondrial Complex IV: Cytochrome c Oxidase
V. Manganese
VI. 3-Acetylpyridine
VII. Myopathies and Myotoxic Agents
VIII. Discussion: What Determines the Regional and Cellular Specificity of Mitochondrial Toxins?
References

SECTION V: NEURODEGENERATIVE DISORDERS
Chapter 10. Parkinson’s Disease
I. Introduction
II. Mitochondrial Dysfunction in Parkinson’s Disease
III. Etiology of Parkinson’s Disease
IV. Mitochondrial Dysfunction and the Pathophysiology of Parkinson’s Disease
V. Concluding Remarks
References

Chapter 11. Huntington’s Disease: The Mystery Unfolds?
I. Huntington’s Disease
II. Epidemiology and Symptomatology
III. Neuropathology
IV. Genetics
V. Other Triplet Repeat Diseases
VI. Intracellular Localization of Normal and Mutant Huntingtin
VII. Function of Normal and Mutant Huntingtin
VIII. Cell Death in Huntington’s Disease: Apoptosis and Autophagy
IX. Oxidative Stress and Metabolic Dysfunction
X. Dopamine Toxicity
XI. Transgenic Mouse Models of Huntington’s Disease
XII. Concluding Remarks
References

Chapter 12. Mitochondria in Alzheimer’s Disease
I. Introduction
II. Historical Overview and the Amyloid Cascade Hypothesis
III. Metabolic Dysfunction in Alzheimer’s Disease has been Reported
IV. Morphological Studies Demonstrate Mitochondrial Abnormalities in Alzheimer’s Disease
V. PDHC and KGDHC in Alzheimer’s Disease
VI. Brain Biochemical Studies of Mitochondrial Enzymes in Alzheimer’s Disease: Is Cytochrome Oxidase
VII. Is a Brain Cytochrome Oxidase Deficiency a Robust Feature of Alzheimer’s Disease?
VIII. Studies of Cytochrome Oxidase in Non-CNS Tissues in Alzheimer’s Disease: Clues to the Origin
IX. Cytochrome Oxidase Dysfunction in Alzheimer’s Disease: Possible Genetic Component?
X. Cytochrome Oxidase Dysfunction in Alzheimer’s Disease: Genetic Studies are Still Inconclusive
XI. Cybrid Data Suggest mtDNA Contributes to Alzheimer’s Disease Cytochrome Oxidase Dysfunction
XII. Unresolved Issues in Alzheimer’s Disease Cybrid Studies: Where is the mtDNA Mutation?
XIII. Could a Cytochrome Oxidase Defect Cause Alzheimer’s Disease?
XIV. Concluding Remarks
References

Chapter 13. Contributions of Mitochondrial Alterations, Resulting from Bad Genes and a Hostile Environment
I. Overview of Neurodegenerative Cascades in Alzheimer’s Disease
II. Mitochondrial Alterations in Alzheimer’s Disease Patients and Experimental Models
III. Genetic Factors and Mitochondrial Alterations in Alzheimer’s Disease
IV. Environmental Factors and Mitochondrial Alterations in Alzheimer’s Disease
V. Conclusions
References

Chapter 14. Mitochondria and Amyotrophic Lateral Sclerosis
I. Introduction
II. Clinical Features
III. Pathogenic Hypotheses
IV. Transgenic Mouse Models of ALS
V. Conclusion
References

SECTION VI: MODELS OF MITOCHONDRIAL DISEASE
Chapter 15. Models of Mitochondrial Disease
I. Introduction
II. Classification of mtDNA Defects Causing Respiratory Chain Disease
III. Cell Models Employed to Study mtDNA Defects
IV. Cell Models of Respiratory Chain Disease Associated with Specific mtDNA Defects
V. Classification of Nuclear DNA Defects Causing Respiratory Chain Disease
VI. Cell Models of Respiratory Chain Disease Associated with Nuclear DNA Defects
VII. Application of Cell Models for the Development of Therapeutic Strategies in mtDNA Disease
VIII. Animal Models of Respiratory Chain Disease
IX. Other Models of Respiratory Chain Disease
X. Conclusions
References

SECTION VII: DEFECTS OF β-OXIDATION INCLUDING CARNITINE DEFICIENCY
Chapter 16. Defects of β-Oxidation Including Carnitine Deficiency
I. Introduction
II. Background Biochemistry
III. Inherited Disorders of Mitochondrial β-Oxidation
IV. Conclusions
References

SECTION VIII: MITOCHONDRIAL INVOLVEMENT IN AGING
Chapter 17. The Mitochondrial Theory of Aging: Involvement of Mitochondrial DNA Damage and Repair
I. Mitochondria: The Biological Clock?
II. Oxidative Damage to Mitochondria
III. Accumulation of Oxidative Damage to mtDNA
IV. DNA Repair in Mammalian Mitochondria
V. Changes in mtDNA Repair with Age
VI. Conclusions
References

Index

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