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)

Angiotensin-converting enzyme (ACE, E.C. 3.4.15.1) has been identified as a normal constituent of human cerebrospinal fluid (CSF). ACE activity in CSF from adult subjects without known neurologic disorder correlated positively (P = 0.002) with age between 50 and 90 years. Patients with moderate degrees of senile dementia of the Alzheimer's type and comparably demented patients with Parkinson's disease or progressive supranuclear palsy exhibited mean levels of ACE activity that were decreased 41, 27 and 53% respectively, compared to the mean level in an age and sex-matched group of neurologically intact individuals. These results raise the possibility that ACE activity in CSF may be an index of neuronal dysfunction in certain central neurodegenerative disorders.
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PMID:Cerebrospinal fluid levels of angiotensin-converting enzyme in Alzheimer's disease, Parkinson's disease and progressive supranuclear palsy. 298 83

Olfactory threshold to differing concentrations of amyl acetate was determined in 78 subjects with idiopathic Parkinson's disease and 40 age-matched controls. Impaired olfactory threshold (previously reported by others) was confirmed in Parkinsonian subjects compared with controls. There was no significant correlation between olfactory threshold and age, sex, duration of disease, or current therapy with levodopa or anticholinergic drugs. In a sub-group of 14 levodopa-treated patients with severe "on-off" fluctuations, no change in olfactory threshold between the two states was demonstrable. Olfactory impairment in Parkinson's disease may involve mechanisms that are not influenced by pharmacologic manipulation of dopaminergic or cholinergic status.
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PMID:Olfactory threshold in Parkinson's disease. 381 60

Ferritin contains the greatest part of the iron found in the brain, and the release of iron stores from ferritin has an essential role in iron-dependent lipid peroxidation. We examined the effect of cultured microglia on iron mobilization from ferritin. Microglia stimulated by phorbol myristate acetate caused the release of iron from ferritin, which was detected by monitoring iron-ferrozine complex formation. This iron mobilization was mediated by microglial superoxide production, as evidenced by the significant inhibitory effect of superoxide dismutase. The role of superoxide was also supported by the close correspondence of cumulative microglial superoxide production, as demonstrated by the MCLA (Cypridina luciferin analogue)-dependent chemiluminescence assay, to the time course of iron release from ferritin. Iron release induced by activated microglia may be partly responsible for the oxidative damage that is thought to occur in Parkinson's disease and other neurodegenerative disorders.
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PMID:Activated microglia cause superoxide-mediated release of iron from ferritin. 762 46

Chronic inflammation associated with the amyloid plaques may represent an acute phase response in the brain. We quantitated the levels of two inflammatory markers; alpha 1-antichymotrypsin (alpha 1-ACT) and interleukin 1 beta (IL-1 beta) in paired serum and cerebrospinal fluid (CSF) samples from 40 patients with Alzheimer's disease (AD), 20 patients with Parkinson's disease (PD), and 42 age-matched controls. No differences in serum or CSF levels of either alpha 1-ACT or IL-1 beta were found between the groups. However, some AD patients had increased alpha 1-ACT index, suggesting an intrathecal production of alpha 1-ACT. Although alpha 1-ACT or IL-1 beta might be involved in the pathogenesis of AD, our results show that their measurement in serum or CSF is not valuable to support the clinical diagnosis of AD.
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PMID:Alpha 1-antichymotrypsin and IL-1 beta are not increased in CSF or serum in Alzheimer's disease. 793 55

There is substantial evidence that estrogens modulate the activity of dopamine in the extrapyramidal system. However, there is conflicting data as to the exact mechanism of estrogen's effects. The majority of clinical reports support an antidopaminergic effect of estrogens on Parkinsonian symptoms. Generally, Parkinsonism worsens with estrogen therapy. We report a case of improvement in Parkinsonian symptoms in a premenopausal patient when placed on leuprolide acetate. The pharmacologic menopause induced by leuprolide acetate leads to a hypoestrogenic state. We hypothesize that the decrease in estrogen improves Parkinson's disease symptoms via the relief of its antidopaminergic effects on the nigrostriatal pathway.
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PMID:Estrogens and Parkinson's disease. 807 37

The metabolic activity of circulating neutrophils from patients with senile dementia of the Alzheimer's type (SDAT) was investigated by a chemiluminescence assay and compared with that of old and young healthy controls. Neutrophils from demented patients showed a higher and faster chemiluminescence emission than those of controls when activated in vitro by autologous or heterologous sera. Granulocytes from patients with Parkinson's disease did not show an increased chemiluminescence activity. Moreover, serum from patients with SDAT depressed the chemiluminescence emission of granulocytes from young donors. Serum levels of alpha 1-antichymotrypsin (alpha 1-ACT) were also determined and were found to be higher in demented subjects than in old and young controls. These data suggest that peripheral and systemic indexes of inflammation are present in the disease and might be associated with mental deterioration.
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PMID:Increased chemiluminescence response of neutrophils from the peripheral blood of patients with senile dementia of the Alzheimer's type. 815 33

We studied nitrogen radical nitric oxide (.NO) release and reactive oxygen species (ROS) production by isolated neutrophils after phorbol myristate acetate (PMA) stimulation in 12 newly diagnosed and nine treated Parkinson's disease (PD) patients and 10 age-matched healthy controls. Neutrophils of both groups of PD patients had an elevated PMA-activated release of .NO [61 and 57%, respectively, higher than that of controls (p < 0.05)]. In contrast, H2O2 release was only significantly increased by 56% in chronically treated patients. In agreement, the maximum rate of luminol-dependent chemiluminescence, which partly represents O2- H2O2- .NO interactions, was increased only in the treated group. When other blood markers of oxidative stress were compared, only erythrocyte catalase activity was decreased in both PD patient series by 33 and 39%, respectively (p < 0.05), whereas plasma antioxidant capacity and erythrocyte superoxide dismutase activity levels were decreased only in treated PD patients. This study suggests that neutrophils express a primary alteration of .NO release in PD patients, whereas H2O2 and oxidative-stress parameters are more probably related to the evolution of PD or to effects of treatment with L-dopa.
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PMID:Neutrophil function, nitric oxide, and blood oxidative stress in Parkinson's disease. 872 42

Microglial activation selectively kills certain neuron populations in mixed neuronal/glial cultures, which may prove useful for modeling neurodegenerative diseases such as Parkinson's disease. In mesencephalic mixed neuronal/glial cultures, microglial activation by zymosan A killed more dopaminergic neurons, assessed by [3H]dopamine uptake and by counting tyrosine hydroxylase-immunoreactive neuron number, than did microglial activation by lipopolysaccharide (LPS). The additional toxicity of zymosan resulted from microglial protein kinase C (PKC) activation. Both zymosan and PMA, but not LPS, activated PKC in enriched microglial preparations. In the mixed neuronal/glial cultures, activation of PKC by phorbol myristate acetate (PMA) increased LPS-induced nitric oxide (NO; by nitrite measurements), but not zymosan-induced NO production, and increased LPS-induced dopaminergic neurotoxicity, but not zymosan-induced dopaminergic neurotoxicity. Additive effects of PMA and LPS, similar to zymosan effects alone, reflected activation of distinct neurotoxic pathways in the microglia. The NO synthase inhibitor N-nitro-L-arginine methyl ester (NAME) totally blocked the neurotoxicity of LPS, and partially blocked zymosan-induced neurotoxicity; NAME did not block the PKC component of neurotoxicity. In addition to stimulating NO production as effectively as LPS, zymosan also activates microglial PKC and associated non-NO-mediated neurotoxic pathways that may be important in human neurodegenerative diseases. Since the role of NO in human microglia-induced neurotoxicity is controversial, zymosan may prove more useful than LPS as a microglial activator in the rodent mixed neuronal/glial culture model.
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PMID:Role of protein kinase C in microglia-induced neurotoxicity in mesencephalic cultures. 905 44

Olfactory evoked potential (OEP) recordings were undertaken using amyl acetate stimulation in 20 patients with Parkinson's disease, nine patients with Alzheimer's disease, seven patients with olfactory dysfunction with no other neurological disorder, and 17 control subjects. In order to eliminate the somatosensory factor from the combined somatosensory and olfactory components produced by amyl acetate stimulation, we substracted the potentials using odorless air from those using amyl acetate. In normal subjects, three components were observed, the mean latencies of which were 309 +/- 46, 484 +/- 61 and 710 +/- 55 ms. In all subjects with anosmia (n = 7), no responses were observed. In the patients with Alzheimer's disease, the components were fewer despite having no olfactory dysfunction. In the 20 patients with Parkinson's disease, eight [corrected] patients showed no components, seven patients showed one component and four [corrected] patients showed two components. The components rarely were detected in spite of whether the patients had olfactory dysfunction or not. Olfactory evoked potentials are useful in detecting olfactory dysfunction and the early stages of Alzheimer's disease and Parkinson's disease.
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PMID:Olfactory evoked potentials in Parkinson's disease, Alzheimer's disease and anosmic patients. 920 69

Although the cause of Parkinson's disease is unknown, oxidative stress has been implicated in its pathogenesis. This theory postulates that normal metabolic processes in the nigrostriatal dopaminergic system may lead to loss of neurons, and that iron-dependent membrane lipid peroxidation may play an important role in the neuronal death. Recent research concerning iron-dependent lipid peroxidation is presented. First, catechols (including dopa and dopamine) and iron form strong oxidizing complexes and induce lipid peroxidation (LPO) in phospholipid liposomes. Active oxygen species including superoxide, hydrogen peroxide, hydroxyl radical and singlet oxygen, do not participate in this LPO, which is inhibited by an excess of dopa (dopamine). Cultured neurons and the substantia nigra are vulnerable to LPO. Second, synthetic melanin prepared by the autooxidation of catechols promotes LPO in the presence of iron. The effects of scavenging agents indicate that this LPO is mediated by superoxide, but not by other oxygen free radicals. Neuronal cell cultures are destroyed by this LPO. Third, catechols and superoxide produced by microglia cause the release of iron from ferritin. Microglia stimulated by phorbol myristate acetate produce superoxide and cause the release of iron from ferritin. Catechols also induce mobilization of ferritin iron. The released iron (i.e. loosely-bound iron) is available to iron-dependent LPO. These data suggest that the biochemical and morphological characteristics of the substantia nigra, which are concomitant with its functional role, provoke iron-dependent lipid peroxidation. It is essential to elucidate how iron bound loosely to low molecules comes into contact with catechols, neuromelanin and superoxide. Drugs that chelate iron site-specifically or modulate the microglial function may bring about some favorable changes in the disease process.
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PMID:[Oxidative stress and the brain]. 943 Sep 79


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