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Cell-cycle mechanisms and neuronal cell death / Agata Copani, Ferdinando Nicoletti. — Georgetown, Tex. : New York, N.Y. : Landes Bioscience / Eurekah.com ; Kluwer Academic/Plenum, c2005.—(64.1/C781)

Contents

        Content
    
1. Cell Cycle Activation in Neurons: The Final Exit of Brain-Morpho-Dysregulation 1
Selective Neuronal Vulnerability: The Key Issue to Understand Neurodegenerative Disorders 1
Plasticity Meets Cell Death 2
Brain-Morpho-Dysregulation and Replay of Developmental Mechanisms 8
Cell-Cycle as an Alternative Effector Pathway of Plasticity-Related Signaling Mechanisms 9
The Cell Cycle Integrates Intercellular and Intracellular Signaling and Links Development, Oncogenesis and Neurodegeneration 12
2. Paved with Good Intentions: The Link between Cell Cycle and Cell Death in the Mammalian Central Nervous System 22
Cell Division 22
Cell Cycle Events in the Cell Death Process 23
The Cell Biology of Cell Cycle Induced Cell Death 24
Human Disease 26
3. The Role of Presenilins in the Cell Cycle and Apoptosis 30
Alzheimer's Disease Pathology 30
Presenilin Structure and Function 31
The Role of Presenilins in Apoptosis 32
Presenilins Apoptosis and the Calcium Connection 34
Presenilins and the Cell Cycle 34
Do Presenilin Genes Have Dual Functions in Cellular Proliferation and Aging? 36
Apoptosis and Alzheimer's Disease 36
4. Cell Cycle Activation and Cell Death in the Nervous System 42
Cell Cycle and Apoptosis in the Developing Nervous System 44
Iatrogenic Neurodegeneration 45
Neurodegenerative Disorders 45
Alzheimer's Disease and Related Dementias 45
Temporal Lobe Epilepsy 48
A Few Words of Caution 49
5. Cell Cycle and Chromosome Segregation Defects in Alzheimer's Disease 55
Trisomy 21 Mosaicism in Alzheimer's Disease 57
Defects in Mitosis in Alzheimer's Disease 58
Potential Mitotic Function of the Presenilin Proteins 60
Nucleoplasm or Cytoplasm 60
Lumen of Nuclear Envelope or Endoplasmic Reticulum 60
Mitotic Effects of the Normal and FAD Mutant Presenilin Proteins in Transfected Cells 64
Chromosome and Cell Cycle Changes in Cells from Presenilin Transgenic and Knockout Mice 64
Mutation/Inactivation of the Tumor Suppressor p53 Causes Chromosome Instability and Regulates Expression of Presenilin 66
Presenilin Mutations May Effect Mitosis in both Neurons and Glia 67
How Aneuploidy May Lead to Alzheimer's Disease 68
Potential Involvement of Other Genes in Chromosome Mis-Segregation in Alzheimer's Disease 68
Implications of Trisomy 21 Mosaicism in Alzheimer's Disease for Future Diagnosis and Therapy 69
6. Alzheimer Disease: A New Beginning or a Final Exit? 79
Pathological Hallmarks of Alzheimer Disease 79
A Mitotic Phenotype Appears in Alzheimer Disease 80
Go Exit, G1 Entry, and Mitogenic Drivers in Alzheimer Disease 81
Apoptotic Avoidance in Alzheimer Disease 82
Redox Imbalance and Cell Cycle Re-Entry 83
7. From Cell Cycle Activation to the Inhibition of the Wnt Pathway: A Hypothesis of How Neurons Die in Response to β-Amyloid 94
The Regulation of the Cell Cycle by A~3 94
The DNA Replication Machinery Activated by Aβ in Adult Neurons 95
Cell Cycle Signaling, DNA Damage and Neuronal Apoptosis 96
Pharmacological Perspectives 98
Index 101