Book contents
- Frontmatter
- Contents
- List of contributors
- Preface
- Part I Basic aspects of neurodegeneration
- 1 Endogenous free radicals and antioxidants in the brain
- 2 Biological oxidants and therapeutic antioxidants
- 3 Mitochondria, metabolic inhibitors and neurodegeneration
- 4 Excitoxicity and excitatory amino acid antagonists in chronic neurodegenerative diseases
- 5 Glutamate transporters
- 6 Calcium binding proteins in selective vulnerability of motor neurons
- 7 Apoptosis in neurodegenerative diseases
- 8 Neurotrophic factors
- 9 Protein misfolding and cellular defense mechanisms in neurodegenerative diseases
- 10 Neurodegenerative disease and the repair of oxidatively damaged DNA
- 11 Compounds acting on ion channels
- 12 The role of nitric oxide and PARP in neuronal cell death
- 13 Copper and zinc in Alzheimer's disease and amyotrophic lateral sclerosis
- 14 The role of inflammation in Alzheimer's disease neuropathology and clinical dementia. From epidemiology to treatment
- 15 Selected genetically engineered models relevant to human neurodegenerative disease
- 16 Toxic animal models
- 17 A genetic outline of the pathways to cell death in Alzheimer's disease, Parkinson's disease, frontal dementias and related disorders
- 18 Neurophysiology of Parkinson's disease, levodopa-induced dyskinesias, dystonia, Huntington's disease and myoclonus
- Part II Neuroimaging in neurodegeneration
- Part III Therapeutic approaches in neurodegeneration
- Normal aging
- Part IV Alzheimer's disease
- Part VI Other Dementias
- Part VII Parkinson's and related movement disorders
- Part VIII Cerebellar degenerations
- Part IX Motor neuron diseases
- Part X Other neurodegenerative diseases
- Index
- References
7 - Apoptosis in neurodegenerative diseases
from Part I - Basic aspects of neurodegeneration
Published online by Cambridge University Press: 04 August 2010
- Frontmatter
- Contents
- List of contributors
- Preface
- Part I Basic aspects of neurodegeneration
- 1 Endogenous free radicals and antioxidants in the brain
- 2 Biological oxidants and therapeutic antioxidants
- 3 Mitochondria, metabolic inhibitors and neurodegeneration
- 4 Excitoxicity and excitatory amino acid antagonists in chronic neurodegenerative diseases
- 5 Glutamate transporters
- 6 Calcium binding proteins in selective vulnerability of motor neurons
- 7 Apoptosis in neurodegenerative diseases
- 8 Neurotrophic factors
- 9 Protein misfolding and cellular defense mechanisms in neurodegenerative diseases
- 10 Neurodegenerative disease and the repair of oxidatively damaged DNA
- 11 Compounds acting on ion channels
- 12 The role of nitric oxide and PARP in neuronal cell death
- 13 Copper and zinc in Alzheimer's disease and amyotrophic lateral sclerosis
- 14 The role of inflammation in Alzheimer's disease neuropathology and clinical dementia. From epidemiology to treatment
- 15 Selected genetically engineered models relevant to human neurodegenerative disease
- 16 Toxic animal models
- 17 A genetic outline of the pathways to cell death in Alzheimer's disease, Parkinson's disease, frontal dementias and related disorders
- 18 Neurophysiology of Parkinson's disease, levodopa-induced dyskinesias, dystonia, Huntington's disease and myoclonus
- Part II Neuroimaging in neurodegeneration
- Part III Therapeutic approaches in neurodegeneration
- Normal aging
- Part IV Alzheimer's disease
- Part VI Other Dementias
- Part VII Parkinson's and related movement disorders
- Part VIII Cerebellar degenerations
- Part IX Motor neuron diseases
- Part X Other neurodegenerative diseases
- Index
- References
Summary
Introduction
Although reports on the morphological characteristics of apoptosis in neurodegenerative diseases remain controversial, accumulating evidence suggests that the molecular and biochemical pathways of apoptosis are involved in neuronal death of various neurodegenerative disorders and in related cellular and animal models. This includes stroke, head trauma, Huntington's (HD), Parkinson's (PD), Alzheimer's disease (AD and amyotrophic lateral sclerosis (ALS)). This evidence includes the activation of the mitogen activated protein (MAP) kinase pathway, the induction of Bax, prostate apoptosis response-4 (Par-4) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), evidence of aberrant activation of the cell cycle machinery, and the activation of caspases. Caspases are the mammalian cell-death-effector proteins. They may have an important role in acute and chronic neurodegenerative diseases. They execute cell death but may also be linked to the initiation of chronic neurodegenerative diseases. Peptide or protein inhibitors of caspases protect neurons in vitro or in animal models of neurological disorders. Although preclinical results are promising, clinical studies have not been performed because of the lack of synthetic caspase inhibitors that cross the blood–brain barrier. Such agents are a major focus in current programs of drug development and will hopefully become available soon. However, in some cell culture and animal models caspase inhibitors block cell death but may result in survival of a dysfunctional neuron. In contrast, therapeutic interference with the signaling phase of apoptosis, e.g. inhibition of the MAP kinase pathway, or the combination of caspase inhibitors with neurotrophins may provide morphological and functional protection.
- Type
- Chapter
- Information
- Neurodegenerative DiseasesNeurobiology, Pathogenesis and Therapeutics, pp. 80 - 93Publisher: Cambridge University PressPrint publication year: 2005