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)

Virological studies were performed on brain material from 9 patients with idiopathic Parkinson disease and 3 matched controls. Electron microscopy and indirect immunofluorescent study were carried out directly on autopsy material from substantia nigra, caudate nucleus, and hypothalamus and on primary tissue culture explants of these brain areas grown alone or in cocultivation with virus-susceptible indicator cell lines. All studies were negative for the presence of viral particles, viral inclusions, or cellular changes suggestive of virus infection. All materials were negative for antigens of herpes simplex type 1, influenza A/NWS, and measles (Edmonston strain) viruses. Within the limits of these tehcniques, there is no evidence at this time that viruses are an important etiological agent in idiopathic Parkinson disease.
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PMID:Search for viral particles and virus-specific products in idiopathic Parkinson disease brain material. 53 25

Disability and progression in Parkinson's disease prior to levodopa treatment was investigated in a random group of 442 patients representing 91 per cent of all known cases with Parkinson's disease in a defined area. Almost half the patients were totally independent, 27 per cent needed help occasionally, and 25 per cent were dependent on other people. Ten per cent of the patients had only unilateral symptoms, 57 per cent had bilateral involvement with mild disability, 20 per cent had a moderately advanced disease, and 13 per cent were severely idsabled. A great variation was found in progression rates. In individual cases, however, the progression rate seemed to be relatively fixed. Concurrent arteriosclerosis was found to worsen the prognosis, whereas the beginning of the disease with tremor and the occurrence of prominent tremor promised a slower progression. Twenty-six patients with only unilateral symptoms 10 years after onset of the disease were found to correspond to postencephalitic patients in age structure, and in such cases a history of preceeding viral infection of the central nervous system was observed on four occasions.
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PMID:Disability and progression in Parkinson's disease. 89 18

The causes of the neurodegenerative disorders of Parkinson's disease (PD), Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS) are unknown. It is proposed that all these disorders result primarily from a loss of trophic peptidergic neurotransmitter, possibly Substance P (SP). This loss in turn produces the classical neuronal degeneration seen in each of these diseases and occurs due to a combination of natural aging and chronic autoimmune destruction following a viral infection of the CNS, early in life. The loss is therefore slow and by the time of clinical presentation the inflammatory process is disappearing as the antigenic stimulus lessens with its removal. The implications of the theory in terms of future research and therapy are briefly discussed.
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PMID:Substance P and neurodegenerative disorders. A speculative review. 172 84

The localization of alpha-interferon (alpha-IFN) and its induced protein, MxA, was examined in human brain tissues from neurologically normal, Alzheimer's disease (AD) and Parkinson's disease (PD) cases. In all cases, a few neurons in the superficial cortical layers and microglial cells in the white matter were stained with the antibody to alpha-IFN. In AD brains, white matter microglia were intensely labeled for alpha-IFN and reactive microglia, such as those on senile plaques, were strongly positive for MxA protein. In PD, Lewy bodies in the substantia nigra were positive for MxA, but there was no staining for alpha-IFN in that region. These results suggest that increased expression of alpha-IFN in the white matter microglia and appearance of MxA protein in reactive microglia contribute to Alzheimer pathology. The staining of some Lewy bodies for MxA may be indicative of a viral infection or other unknown factor.
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PMID:Immunohistochemistry using antibodies to alpha-interferon and its induced protein, MxA, in Alzheimer's and Parkinson's disease brain tissues. 789 72

Using a case-control method, we studied the role of environmental risk factors and viral infection in the development of Parkinson's disease (PD) in China. Ninety-three PD patients and 186 controls were investigated with a questionnaire and from most of them, blood was taken to test the antibody levels of four virus (measles, rubella, HSV-1, CMV) IgG. The study result showed that positive family history, living near rubber plants, drinking river-water were associated with an increased risk of developing PD. In contrast, living in small cities, drinking well-water, drinking hard-liquor frequently, were associated with a decreased risk for PD. PD cases and controls did not differ with respect to other factors investigated including smoking and viral infection. These findings suggest that some environmental factors may be related to the development of PD, but further standardized studies will be required to confirm our results.
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PMID:A case-control study on the environmental risk factors of Parkinson's disease in Tianjin, China. 827 80

Several lines of evidence indicate an immune-mediated pathophysiology of Parkinson's disease (PD) and Alzheimer's disease (AD). In clinical studies the monoamine oxidase-B inhibitor Selegiline appears to slow the progression of neurological deficits in PD and the cognitive decline in AD. The immune response to bacterial or viral infection and in chronic inflammatory processes is stimulated by an increased synthesis of the cytokines interleukin-1 beta (IL-1 beta) and subsequently interleukin-6 (IL-6). We investigated the influence of Selegiline on the synthesis of IL-1 beta and IL-6 in peripheral blood mononuclear cells (PBMC) from healthy blood donors cultured with or without Selegiline (10(-8)M, 10(-9)M or 10(-10)M) in a humidified atmosphere (7% CO2). Treatment of cultured PBMC with Selegiline significantly increased synthesis of both cytokines. The effect of Selegiline on cytokine biosynthesis may contribute to its putative neuroprotective properties.
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PMID:Selegiline stimulates biosynthesis of cytokines interleukin-1 beta and interleukin-6. 911 94

For the past 40 years, research into Parkinson's disease (PD) has been predominantly the province of epidemiologists interested in pursuing the connection between the disease and environmental factors such as viral infection or neurotoxins. Hereditary influences were actually discounted because of a high monozygotic twin discordance rate found in studies that were later shown to be inadequate and inconclusive. There has recently been a resurgence of interest in investigating hereditary factors in PD when it became more and more apparent that a positive family history was a major risk factor for the disease. Meanwhile, it also became increasingly apparent from neuropathological studies that the common, idiopathic form of Parkinson's disease had, in fact, a pathological correlate, i.e., the existence of Lewy bodies, an eosinophilic cytoplasmic inclusion body, distributed diffusely throughout the substantia nigra, hypothalamus, hippocampus, autonomic ganglia and olfactory tracts. Although candidate gene approaches to linkage in PD families have not been rewarding, a genome wide scan mapped PD to 4q21-23 in one large family with PD with diffuse Lewy bodies, where a candidate gene, alpha-synuclein, resides. This gene encodes a presynaptic protein of which a peptide fragment is known to be a constituent of Alzheimer's disease plaques. The identification of a missense mutation in the alpha-synuclein gene in four independent PD families suggests that at least some fraction of familial PD with diffuse Lewy bodies is the result of an abnormal protein that interferes with normal protein degradation leading to the development of inclusions and ultimately neuronal cell death. There may be common pathogenetic mechanisms involved in alpha-synuclein mutations in PD and beta-amyloid and presenilin gene mutations in Alzheimer's disease.
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PMID:Genetics of Parkinson's disease. 930 Jun 60

In clinical studies the MAO-B inhibitor selegiline appears to slow the progression of neurological deficits in Parkinson's disease (PD) and the cognitive decline in Alzheimer's disease (AD). The mechanisms of action remain unclear. Several lines of evidence indicate an immune-mediated pathophysiology of PD and AD. According to animal trials, selegiline increases the survival rate of immune suppressed mice. Stimulation of the immune response to bacterial or viral infection or in chronic inflammatory processes in managed by an increased synthesis of the cytokines interleukin-1 beta (IL-1 beta) and subsequent interleukin-6 (IL-6). Outcome of viral or bacterial infections in the brain highly correlates with levels of the cytotoxic cytokine tumor-necrosis-factor-alpha (TNF). The aim of our study was to characterize the influence of selegiline on the biosynthesis of IL-1 beta, IL-6 and TNF in human peripheral blood mononuclear cells (PBMC) from healthy blood donors. After isolation and washing PBMC were cultured without and with selegiline in three different concentrations (0.01 mumol/l, 0.001 mumol/l, 0.0001 mumol/l) in a humidified atmosphere (7% CO2). Then cultures were centrifuged and supernatants were collected for IL-1 beta, IL-6 and TNF ELISA-assays. Treatment of cultured PBMC with various concentrations induced an increased synthesis of IL-1 beta (ANOVA F = 9.703, p = 0.0007), IL-6 (ANOVA F = 20.648, p = 0.0001) and a reduced production of TNF (ANOVA F = 3.770, p = 0.040). These results indicate, that the influence of selegiline on the cytokine biosynthesis may also contribute to its putative neuroprotective properties.
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PMID:Selegiline as immunostimulant--a novel mechanism of action? 956 33

Neurotrophic factors may be valuable for improving the survival and the functional efficacy of fetal nigral grafts to treat Parkinson's disease (PD). However, further characterization of their effects is required. New methods of protein delivery also need to be explored to supply sustained and regulated levels of these molecules. Gene transfer via adenoviral vectors is a promising strategy for this purpose. We show herein the effect of adenovirus-mediated transforming growth factor beta1 (TGFbeta1) gene transfer on fetal nigral grafts in a rat model of PD. Direct injection of AdTGFbeta1 into the dopamine-depleted striatum decreased the survival of the transplanted tyrosine hydroxylase-positive (TH+) neurons and impaired the functional efficacy of grafts. Viral toxicity to the graft was avoided by separating the site of viral infection from the transplant by a distance that allowed TGFbeta1 effect on the graft. This infection protocol may be useful for delivering secreted molecules with neurotrophic effects to dopaminergic grafts.
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PMID:Adenovirus-mediated over-expression of TGFbeta1 in the striatum decreases dopaminergic cell survival in embryonic nigral grafts. 1042 93

Viral vectors have recently been used successfully to transfer genes and express different proteins in the brain. This review discusses the requirements to consider human clinical trials in which recombinant adeno-associated virus vectors are used to transfer the genes necessary to produce l-dihydroxyphenylalanine (l-dopa) directly into the striatum of Parkinson's patients. Preclinical data that apply to the criteria defined as prerequisite for clinical trials are discussed. Thus, in animal models using recombinant adeno-associated virus vectors it has been demonstrated that l-dopa can be synthesized in the striatum after in vivo transduction. In addition, these l-dopa levels are sufficient to affect behavior in a dopamine-deficient animal model, the expression is extremely long-lasting, and the ability to transcriptionally regulate tyrosine hydroxylase has been demonstrated but not fully characterized. However, while immune responses to recombinant adeno-associated virus infection in the periphery have been studied, direct assessment of the potential immune response in the brain has not been sufficiently defined. Therefore, the rationale for delivering l-dopa directly to the striatum to treat Parkinson's disease is sound and the preclinical data are promising but all the issues surrounding this strategy are not resolved.
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PMID:Progress in direct striatal delivery of L-dopa via gene therapy for treatment of Parkinson's disease using recombinant adeno-associated viral vectors. 1048 74


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