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
9 - Protein misfolding and cellular defense mechanisms 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
In many major neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), Alzheimer's disease, Parkinson's disease, and several hereditary diseases caused by expansions of polyglutamine (PolyQ) tracts (e.g. Huntington's disease and the spinocerebellar ataxias) (Table 9.1), the pathology and the eventual death of specific neuronal populations occur due to the accumulation of specific abnormal polypeptides, which form insoluble intracellular inclusions. Many observations suggest that these various types of inclusions arise through common mechanisms and elicit similar host responses. For example, all these inclusions contain components of the ubiquitin-proteasome degradation pathway and also molecular chaperones, which represent the two main systems that eukaryotic cells use to protect themselves against the buildup of unfolded polypeptides. The accumulation of abnormal polypeptides in the form of inclusions in various neurological disorders must result from an inability of neurons to either refold or degrade these abnormal species. Because these neurological diseases are of late onset, and the very same mutant proteins are expressed without causing obvious pathology in younger individuals, it seems likely that the failure to adequately deal with these abnormal molecules progresses with aging.
Because the continued accumulation of unfolded, non-functional polypeptides is likely to cause cell toxicity, it is not surprising that defense mechanisms emerged early in evolution that enable cells to withstand the appearance of large amounts of unfolded proteins, as may result from mutations, errors in protein synthesis, or inefficient folding of nascent polypeptides.
- Type
- Chapter
- Information
- Neurodegenerative DiseasesNeurobiology, Pathogenesis and Therapeutics, pp. 108 - 130Publisher: Cambridge University PressPrint publication year: 2005