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)

S-Adenosylmethionine is an essential ubiquitous metabolite central to many biochemical pathways, including transmethylation and polyamine biosynthesis. Reduced CSF S-adenosylmethionine levels in Alzheimer's disease have been reported; however, no information is available regarding the status of S-adenosylmethionine or S-adenosylmethionine-dependent methylation in the brain of patients with this disorder. S-Adenosylmethionine concentrations were measured in postmortem brain of 11 patients with Alzheimer's disease. We found decreased levels of S-adenosylmethionine (-67 to -85%) and its demethylated product S-adenosylhomocysteine (-56 to -79%) in all brain areas examined (cerebral cortical subdivisions, hippocampus, and putamen) as compared with matched controls (n = 14). S-Adenosylmethionine and S-adenosylhomocysteine levels were normal in occipital cortex of patients with idiopathic Parkinson's disease (n = 10), suggesting that the decreased S-adenosylmethionine levels in Alzheimer's disease are not simply a consequence of a chronic, neurodegenerative condition. Reduced S-adenosylmethionine levels could be due to excessive utilization in polyamine biosynthesis. The severe reduction in levels of this essential biochemical substrate would be expected to compromise seriously metabolism and brain function in patients with Alzheimer's disease and may provide the basis for the observations of improved cognition in some Alzheimer's patients following S-adenosylmethionine therapy.
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PMID:Brain S-adenosylmethionine levels are severely decreased in Alzheimer's disease. 875 43

The occurrence of movement disorders and particularly Parkinsonian symptoms is uncommon in patients with multiple sclerosis (MS) despite the rather frequent presence of demyelinating plaques in the basal ganglia. This disparity between the occurrence of clinical symptoms in MS and the distribution of demyelinating plaques suggests that impairment of neurotransmitter functions rather than demyelination may be critical to the clinical manifestations of the disease. A 48 year old woman with remitting-progressive MS developed a bilateral Parkinsonian syndrome in association with acute emotional stress which resolved after she received two brief successive extracerebral applications of low frequency picotesla flux density electromagnetic fields (EMFs). It is believed that in this patient Parkinsonism may have existed in a subclinical form and that acute stress, which previously has been shown to precipitate symptoms of Parkinson's disease, triggered the onset of Parkinsonism by further reducing dopaminergic and serotonergic neurotransmission in the basal ganglia. The rapid reversal of the Parkinsonian syndrome by EMFs was related to a presumed augmentation of dopaminergic and serotonergic neurotransmission which, on the basis of CSF studies, is reduced in chronic MS patients. The efficacy of EMFs in the treatment of Parkinson's disease had been documented previously but this report demonstrates that this treatment modality is beneficial also for the treatment of Parkinsonism developing in the setting of other neurodegenerative disorders.
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PMID:Reversal of an acute parkinsonian syndrome associated with multiple sclerosis by application of weak electromagnetic fields. 882 58

Parkinson's disease (PD) is an age-related neurodegenerative movement disorder of unknown etiology. In PD immune abnormalities were reported, but the cause of such abnormalities has not been resolved. Recently, the increased proportion of gamma delta + T cells out of all T cells has been found in patients with PD. Heat shock proteins (hsps) could be targets for gamma delta + T lymphocytes. We examined serum and CSF of patients with PD, age-matched patients with other non-inflammatory neurological diseases (OND old), young patients with other non-inflammatory neurological diseases (OND young), and donors of blood (DB). Antibodies were detected using the enzyme-linked immunosorbent assay. The plates were coated with recombinant mycobacterial hsp 65 and hsp 70. The present study showed that the mean ELISA ratio of CSF from patients with PD was significantly greater than that of CSF from patients with OND old (tested against IgG anti-hsp 65 and IgG anti-hsp 70) and OND young (tested against IgG anti-hsp 70). There was no difference between the mean ELISA ratio of sera from patients with PD, OND old and OND young (tested against IgG anti-hsp 65 and IgG anti-hsp 70). The significance of hsps immunity is not completely clear. Increased hsps expression, which is induced by stress, provides cells with protection against the environmental insults. Alternatively, the antibodies may be present as a consequence of prior infections.
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PMID:Humoral response to hsp 65 and hsp 70 in cerebrospinal fluid in Parkinson's disease. 883 74

We measured beta-carbolinium cations (BC+s) endogenous analogs of the N-methyl-4-phenylpyridinium ion (MPP+), in the lumbar CSF of 22 patients with idiopathic Parkinson's disease (PD) and 11 age-matched controls without any symptoms of parkinsonism. Among the BC+s, 2,9-diemethylnorharmanium cation (2,9-Me2NH+), the most potent neurotoxicant that mirrors MPP+ in mitochondria toxicity, was present in 12 patients with PD but not in controls. Although the 2-monomethylated beta-carbolinium cations (2-MeBC+s), which were present in almost all subjects, registered a slightly higher level in PD patients than in controls, the difference was not significant. The total BC+ content, sum of 2-MeBC+ and 2,9-Me2NH+ levels, was significantly higher in PD patients than in controls. The 2-MeBC+ contents significantly increased with the progression of the PD, but 2,9-Me2NH+ decreased as the disease exacerbated, although levels varied within a wide range. The present results strongly support the hypothesis that "bioactivated" BC+s, especially 2,9-Me2NH+s, may be the endogenous causative factors underlying PD.
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PMID:beta-Carbolinium cations, endogenous MPP+ analogs, in the lumbar cerebrospinal fluid of patients with Parkinson's disease. 884

We measured the CSF and plasma levels of glutamate, glutamine, aspartate (only in plasma), asparagine, glutamine, glycine and GABA in 31 patients with Parkinson's disease and in 45 matched controls. We used an ion-exchange chromatography method. When compared to controls, PD patients had similar CSF levels of glutamate, glutamine, asparagine, and glycine higher CSF GABA levels higher plasma levels of glutamine, asparagine, and glycine, and lower plasma levels of aspartate. The CSF levels of the amino acids measured were not correlated with the clinical features of PD. Our results that CSF GABA levels are not decreased in PD as previously suggested.
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PMID:Neurotransmitter amino acids in cerebrospinal fluid of patients with Parkinson's disease. 888 Jun 90

A very early event in the pathogenesis of idiopathic Parkinson's disease (PD) has been proposed to be an elevated translocation of L-cysteine (CySH) and/or glutathione (GSH) into pigmented dopaminergic cell bodies in the substantia nigra (SN) in which cytoplasmic dopamine (DA) is normally autoxidized to DA-o-quinone as the first step in a reaction leading to black neuromelanin polymer. Such an elevated influx of CySH and GSH would be expected to initially result in formation of 5-S-cysteinyldopamine (5-S-CyS-DA) and 5-S-glutathionyldopamine (5-S-Glu-DA), respectively, and might account for the massive irreversible loss of GSH and progressive depigmentation of SN cells that occurs in the Parkinsonian brain. However, 5-S-Glu-DA has not been detected in the Parkinsonian brain. Furthermore, although the 5-S-CyS-DA/DA and 5-S-CyS-DA/homovanillic acid concentration ratios increase significantly in the SN and cerebrospinal fluid, respectively, of PD patients, the absolute concentrations of 5-S-CyS-DA are extremely low and similar to those measured in age-matched control patients. One explanation for these observations is that 5-S-CyS-DA might be intraneuronally oxidized to more complex cysteinyldopamines and a number of dihydrobenzothiazines (DHBTs) and benzothiazines (BTs). Similarly, 5-S-Glu-DA might be intraneuronally oxidized to more complex glutathionyldopamines. In this investigation, however, it is demonstrated that 5-S-Glu-DA is rapidly metabolized in rat brain to 5-S-CyS-DA and 5-S-(N-acetylcysteinyl) dopamine (5) in reactions mediated by gamma-glutamyl transpeptidase (gamma-GT) and cysteine conjugate N-acetyltransferase. Similarly, 5-S-CyS-DA is metabolized to 5 in rat brain although more slowly than 5-S-Glu-DA. These reactions occur most rapidly in the midbrain, a region that contains the SN. Furthermore, 5, 2-S-(N-acetylcysteinyl)dopamine (6) and 2,5-di-S-(N-acetylcysteinyl)-dopamine (9) are toxic when administered into mouse brain having LD50 values of 14, 25, and 42 micrograms, respectively, and evoke a profound hyperactivity syndrome. These results suggest that the failure to detect 5-S-Glu-DA and the presence of only very low levels of 5-S-CyS-DA in Parkinsonian SN tissue and CSF might be related to both their intraneuronal oxidation and extraneuronal metabolism to N-acetylcysteinyl conjugates of DA. Furthermore, the toxic properties and neurobehavioral responses evoked by 5, 6, and 9 raise the possibility that these N-acetylcysteinyl conjugates of DA, in addition to certain cysteinyldopamines, DHBTs and BTs, might include endotoxins that contribute to SN cell death and other neuronal damage that occurs in PD. Methods are described for the synthesis of several N-acetylcysteinyl conjugates of DA, and their redox behaviors have been studied using cyclic voltammetry.
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PMID:Synthesis, redox properties, in vivo formation, and neurobehavioral effects of N-acetylcysteinyl conjugates of dopamine: possible metabolites of relevance to Parkinson's disease. 890 66

Transforming growth factor (TGF)beta plays a role in injury repair in sites surrounding brain injury. The present study tested the hypothesis that TGFbeta1 and TGFbeta2 levels in the postmortem CSF of patients with neurodegenerative disorders would be elevated compared to those in normal subjects. Free TGFbeta1 and total TGFbeta2 were measured by ELISA in postmortem ventricular cerebrospinal fluid (vCSF) of patients with Parkinson's disease (n = 30), Alzheimer's disease (n = 30), multiple sclerosis (n = 15), and schizophrenia (n = 12) and of normal controls (n = 16). In addition, albumin, IgG, and total protein in vCSF were measured. Both TGFbeta1 and TGFbeta2 were significantly different between groups (P < 0.002 and P < 0.001, respectively). Parkinson's disease vCSF showed significant increases in both TGFbeta1 (P = 0.015) and TGFbeta2 (P = 0.012) compared to normal controls. There was a trend for TGFbeta2 to be elevated in Alzheimer's disease and multiple sclerosis vCSFs, which failed to achieve significance. There were no differences between controls and schizophrenics in TGFbeta1 or TGFbeta2. Alzheimer's disease vCSF showed a significant decrease in protein compared to all other groups, which was not related to blood-brain barrier permeability, age, or autolysis differences. Evidence is presented suggesting that some TGFbeta1 may leak into the vCSF from plasma. Autopsy vCSF levels of TGFbeta isoforms were found to be distinctly different from those reported for human serum, especially for TGFbeta2, which is undetectable in plasma. These results indicate that further in vivo studies of TGFbeta2 in the CSF of Parkinson's disease patients are warranted to determine the relationship between clinical status, medication, and TGFbeta2 concentrations.
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PMID:TGFbeta1 and TGFbeta2 concentrations are elevated in Parkinson's disease in ventricular cerebrospinal fluid. 893 62

In a prospective series of symptomatic adult hydrocephalus characterized by gait disturbance, cognitive impairment, and/or urinary incontinence, 88 of 118 patients (75%) had additional akinetic, tremulous, hypertonic, or hyperkinetic movement disorders. Their prevalence was highest in patients with idiopathic normal pressure hydrocephalus (NPH) of the elderly (56/65 patients, 86%), and they were less frequent in patients with secondary NPH (10/15, 66%), with nonhydrodynamic atrophic/other hydrocephalus (20/33, 61%), and with obstructive hydrocephalus/aqueductal stenosis (2/5, 40%). Akinetic symptoms were found in 73 of 118 patients (62%), and the most frequent movement disorder was upper extremity bradykinesia (55%). Akinetic, tremulous, hypertonic, and hyperkinetic movement disorders were exclusively secondary to causes not related to hydrocephalus in 24 of 118 patients (20%). The proportion of patients with movement disorders not attributable to only such causes was highest in the idiopathic NPH group (44/65, 68%). Thirteen of 118 patients (11%) presented with a parkinsonian syndrome. There was evidence for coexistent Parkinson's disease in four of these patients. Parkinsonism was found to be secondary to NPH in five patients and was found improved after shunting. Akinetic symptoms in patients with NPH generally responded favorably to CSF diversion, which was evident in 80% of a subset of this group. Various other movement disorders did not show definite improvement. The high prevalence of bradykinesia and other akinetic symptoms in NPH and the beneficial effect of shunting on such symptoms suggest that NPH may cause a more generalized disorder of motor function.
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PMID:Movement disorders in adult hydrocephalus. 899 54

We measured the CSF levels of 21, and the plasma levels of 26, amino acids in 31 patients with Parkinson's disease (PD) and in 45 matched controls. We used an ion-exchange chromatography method. When compared to controls, PD patients had lower CSF levels of taurine, alanine, valine, leucine, isoleucine, ethanolamine, citrulline, ornithine, lysine, histidine, arginine, and alpha-aminobutyric acid. PD patients not treated with levodopa or with dopamine agonists had higher CSF tyrosine and phenylalanine levels than those not treated with these drugs and also than controls. PD patients had higher plasma levels of phosphoserine, threonine, methionine, tyrosine, sarcosine and alpha-aminoadipic acid, and lower plasma levels of valine, leucine, and tryptophan, than controls. The CSF/plasma ratio of many of these amino acids was significantly lower in PD patients than those of controls, suggesting that PD patients might have a dysfunction in the transport of neutral and basic amino acids across the blood-brain barrier.
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PMID:Decreased cerebrospinal fluid levels of neutral and basic amino acids in patients with Parkinson's disease. 926 38

We compared CSF and serum levels, and the CSF/serum ratio of alpha-tocopherol (vitamin E), measured by HPLC, in 34 patients with Parkinson's disease (PD) and 47 controls. CSF and serum vitamin E levels were correlate. The mean CSF and serum vitamin E levels, and the CSF/serum ratio of PD patients did not differ significantly between the groups. There was no influence of antiparkinsonian therapy on CSF vitamin E levels. CSF vitamin E levels did not correlate with age, age at onset, duration of the disease, scores of the Unified Parkinson Disease Rating Scale of the Hoehn and Yahr staging in the PD group. These results suggest that CSF vitamin E concentrations are unrelated with the risk for PD.
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PMID:Cerebrospinal fluid levels of alpha-tocopherol (vitamin E) in Parkinson's disease. 950 74


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