Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The hypothesis is that Alzheimer's disease, Parkinson's disease (PD), and motoneurone disease are due to environmental damage to specific regions of the central nervous system and that the damage remains subclinical for several decades but makes those affected especially prone to the consequences of age-related neuronal attrition. This proposal is based on the association between environmental factors and certain neurodegenerative diseases (eg, methylphenyltetra-hydropyridine and parkinsonism, poliovirus infection and post-poliomyelitis syndrome, chickling pea ingestion and lathyrism, an unidentified environmental factor and amyotrophic lateral sclerosis-PD complex of Guam, and trauma and pugilist's encephalopathy) and on the long latent period between exposure to environmental factor and the appearance of symptoms in some of these disorders. The practical implications of this hypothesis are that epidemiological attention should be focussed on the environment in early rather than late life, prevention may be a realistic goal if the cause of subclinical damage can be identified, a search should be undertaken for causal mechanisms linking subclinical neuronal damage due to an environmental factor and the normal ageing process, and (4) better understanding of the regional selective vulnerability of the nervous system to the ageing process might allow a rational approach to treatment.
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PMID:Alzheimer's disease, Parkinson's disease, and motoneurone disease: abiotrophic interaction between ageing and environment? 287 27

This paper presents a rationale for acoustic analysis of voices of neurologically diseased patients, and reports preliminary data from patients with myotonic dystrophy, Huntington's disease, Parkinson's disease, and amyotrophic lateral sclerosis, as well as from individuals at risk for Huntington's disease. Noninvasive acoustic analysis may be of clinical value to the otolaryngologist, neurologist, and speech pathologist for early and differential diagnosis and for documenting disease progression in these various neurologic disorders.
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PMID:Acoustic analysis of voices of patients with neurologic disease: rationale and preliminary data. 296 42

The nervous system is a rich source of filamentous proteins that assume critical roles in determining and maintaining neuronal form and function. Neurons contain three major classes of these cytoskeletal organelles: microtubules, intermediate filaments, and microfilaments. They also contain a variety of proteins that organize them and serve to connect them with each other. Such major neurodegenerative diseases as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, as well as a variety of toxic neuropathies, are characterized pathologically by intraneuronal filamentous inclusions. Recent studies using biochemical and immunocytochemical techniques have established that these abnormalities represent disorganized states of the neuronal cytoskeleton and have determined some of the specific molecular constituents of these inclusions. This knowledge has led to new ways of thinking about their origins.
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PMID:Cytoskeletal protein abnormalities in neurodegenerative diseases. 300 39

Studies of the amyotrophic lateral sclerosis parkinsonism dementia complex of Guam direct suspicion to a heat-labile component of vegetables found in greatest concentration in seeds. We therefore surveyed patients with Parkinson's disease (PD) regarding early adult consumption of fruits and vegetables usually eaten raw, with seeds that are swallowed or scraped with the teeth. We administered a pretested questionnaire by telephone to 81 nondemented patients with PD and to a same-sex married sibling without PD. The patients and their siblings were asked whether they or their spouse (as an internal standard) had been more likely to eat each of 17 food items between marrying and age 40 years. No item was associated with the presence of PD. Unexpectedly associated with the absence of PD were preference for nuts (odds ratio, 0.39), salad oil or dressing (pressed from seeds) (odds ratio, 0.30), and plums (odds ratio, 0.24). These three items have higher vitamin E content than the other 14 items in our questionnaire. Our data are consistent with the hypothesis that vitamin E, as an antioxidant, may have prophylactic value against PD.
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PMID:Case-control study of early life dietary factors in Parkinson's disease. 319 95

We report 5 cases of bilateral abductor paralysis of the vocal cords (Gerhardt syndrome) with attacks of nocturnal asphyxia in patients with Parkinson disease, Shy-Drager syndrome, amyotrophic lateral sclerosis and tumor of the posterior cranial fossa.
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PMID:Bilateral abductor paralysis of the vocal cords in the course of neurological diseases: report of 5 cases. 335 25

The origin of degenerative diseases of the central nervous system lies in genetic and acquired disorders. Analysis of the clinical characteristics of diseases affecting specific neuronal systems may help us to understand their pathogenesis. The stereotyped symptomatology characteristic of most degenerative diseases results from neuronal death in specific pathways: pyramidal tract and motor neurons in amyotrophic lateral sclerosis, nigrostriatal dopamine system in Parkinson's disease, posterior and lateral columns of the spinal cord in Friedreich's ataxia, etc. This suggests that these neurons are sensitive to pathological processes that are still unknown. Progression of the disease, whether linear or not, is slow, but it is more rapid than similar effects due to ageing. This indicates either that the environmental cause of degeneration (if it exists) is continuously present or that a vital process has been once and for all disrupted, perhaps at the level of the genome, causing insufficient production of essential proteins, or accumulation of eventually toxic metabolites. Symptoms generally appear during adulthood, i.e. after normal differentiation has taken place, and after a considerable number of neurons have already been damaged. The initiation of neuronal death precedes the appearance of the first symptoms.
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PMID:Nerve cell death in degenerative diseases of the central nervous system: clinical aspects. 355 87

The human neurological disorders--amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), and Alzheimer's disease (AD)--share certain features: they occur in later stages of adult life; are slowly progressive; and involve specific groups of nerve cells. Different clinical syndromes result from dysfunction and death of these specific groups of neurons. In ALS, patients are weak due to disease of motor neurons in the spinal cord. The clinical features of PD, e.g. slow movements, tremor and rigidity, are attributed, in part, to degeneration of dopaminergic neurons of the substantia nigra. Impairments of cognition and memory in AD result from disease of neurons in a number of regions, including brainstem, basal forebrain, amygdala, hippocampus, and neocortex. In each of these diseases, affected neurons exhibit abnormalities of the neuronal cytoskeleton: in ALS, neurofilaments accumulate and distend proximal motor axons; in PD, nigral perikarya show Lewy bodies-intracytoplasmic inclusions containing neurofilament antigens; in AD, neurons develop neurofibrillary tangles, Hirano bodies, granulovacuolar degeneration and filament-filled neurites in plaques. Certain features of ALS, PD and AD are recapitulated in animal models, three of which are described in this review. Hereditary canine spinal muscular atrophy (HCSMA), a dominantly inherited motor neuron disease, shows many clinical and pathological features in common with ALS, including weakness, muscle atrophy, neurofilamentous swellings of proximal axons, impaired transport of neurofilament proteins, and degeneration of motor neurons. In primates, intoxication with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces a parkinsonian syndrome due to injury of nigral dopaminergic neurons and associated denervation of the striatum. Finally, aged macaques exhibit memory deficits, and their cerebral cortices show senile plaques and filament-filled neurites derived from a variety of transmitter-specific populations of nerve cells. In human diseases, the causes and mechanisms leading to dysfunction and death of nerve cells are unknown. Investigators have begun using a variety of techniques derived from neurobiology to study animal models in an effort to clarify the mechanisms, evolutions, and consequences of structural-chemical abnormalities occurring in different neuronal systems implicated in human disease. Understanding such processes in these models should provide important new insights into the pathogeneses of similar processes occurring in ALS, PD and AD.
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PMID:Dysfunction and death of neurons in human degenerative neurological diseases and in animal models. 355 88

Amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), and Alzheimer's disease (AD) are human neurological disorders which occur in middle and late life. These three diseases share certain features: they are slowly progressive; transmitter-specific groups of neurons are selectively affected by disease processes; and affected nerve cells exhibit cytoskeletal pathology. The causes and mechanisms of cell injury are unknown, and there are no treatments which directly affect the disease process. Dysfunction and death of these specific cell groups account for different clinical syndromes. In ALS, patients become paralyzed, at-risk cholinergic motor neurons in the spinal cord develop neurofilamentous swellings of proximal axons, and distal axons atrophy. In PD, affected individuals show slowed movements, tremor, and rigidity. These clinical findings are attributed to regeneration of dopaminergic neurons of the substantia nigra, a cell group showing abnormal accumulations of neurofilament antigens in the form of Lewy bodies. In AD, patients develop dementia (a syndrome of cognitive and memory impairment), and cholinergic neurons of the basal forebrain and certain other populations of nerve cells develop abnormalities of the cytoskeleton. These include perikaryal neurofibrillary tangles and enlarged distal axons which appear as neurites in senile plaques. Certain features of ALS, PD, and AD are recapitulated in three animal models described in this review. Hereditary Canine Spinal Muscular Atrophy (HCSMA), a dominantly inherited motor neuron disease, shows many clinical and pathological features in common with ALS. Affected dogs are clinically weak, have denervation atrophy of muscles, and develop neurofilamentous swellings of proximal axons, atrophy of distal axons, and degeneration of motor neurons. These abnormalities of axonal caliber are associated with impaired transport of the neurofilament triplet proteins and a maldistribution of phosphorylated neurofilaments. Intoxication of macaques with 1-methyl-4-]henyl-1,2,3,6,tetrahydropyridine (MPTP) produces a Parkinsonian syndrome due to selective injury of dopaminergic neurons in the substantia nigra and associated denervation of the striatum. Finally, aged rhesus monkeys (older than 23 years of age) show cognitive and memory deficits and exhibit senile plaques whose neurites are derived from cholinergic and other transmitter systems. Although these macaques do not have AD, they do provide a model for examining the relationships between age-associated cognitive deficits and pathological changes occurring in certain transmitter systems of primates.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Animal models of degenerative neurological disease. 360 87

Mortality rates for deaths "due to" and "with" motor neuron disease are presented for the first time. Age-specific mortality rates increase with age until 70 to 74 years and then decline. There appear to be no major differences by race in the age-adjusted mortality rates, but these rates are higher for males both white and nonwhite. A case-control study of all deaths with amyotrophic lateral sclerosis (ALS) was conducted for deaths due to ALS in the year 1971. Conditions associated with ALS at the time of death include pneumonia and bronchopneumonia, symptoms referable to respiratory system, superficial injury to shoulder and upper arm, essential benign hypertension, chronic skin ulcer, and malnutrition. No association was found between ALS and malignancies, Parkinson's disease, or dementia.
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PMID:Motor neuron disease in the United States, 1971 and 1973-1978: patterns of mortality and associated conditions at the time of death. 361 53

Progressive degeneration of functionally related groups of neurons occurs in certain infective, toxic, nutritional and genetically determined neurological diseases. It also takes place in normal aging, and several of the regions that undergo selective decay with the passage of time seem to be the same target regions that are afflicted in degenerative disorders such as Parkinson's disease. Alzheimer's disease and amyotrophic lateral sclerosis (ALS). Infective etiology is relatively easy to exclude by a combination of immunological tests and transfer experiments. Genetic causation can be rendered unlikely when large kindreds are available for study. Nutritional deprivation and acute or subacute toxicity are accessible to explanation by examining the environment. The most difficult mechanism of pathogenesis to refute is chronic toxic damage, where the lesion may derive from long-term exposure to a relatively widespread noxious agent or agents. Variations in involvement of individuals within a population may stem from differing capacities to activate or inactivate a toxin. Inherent in this concept of etiology is recognition that compensatory potential within the central nervous system may contribute to prolonged existence of subclinical lesions so that a latent period may exist for several decades, between causal event and the onset of symptoms. Furthermore, progressive clinical deterioration may take place even though the cause may have been transient, many years before.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Aging of the nigrostriatal pathway in humans. 367 18


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