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)

Several recent studies have shown decreased copper and increased zinc concentrations in the substantia nigra and increased copper concentrations in the cerebrospinal fluid of Parkinson's disease patients. To elucidate whether changes in serum levels of these trace elements may increase the risk of developing Parkinson's disease (PD), we assessed serum levels of zinc and copper by flame atomic absorption spectrophotometry, and albumin and ceruloplasmin, in 32 (Zn) and 39 PD patients (Cu), respectively, with their spouses as the control group. Serum zinc, albumin, copper and ceruloplasmin levels and the zinc/albumin and copper/ceruloplasmin ratios, did not differ significantly between the two groups and were not influenced by antiparkinsonian therapy in the PD patients. Serum zinc/albumin ratio (r = 0.43), ceruloplasmin (r = -0.36) and copper/ceruloplasmin ratio (r = 0.36) correlated significantly with age, but not with age of onset, duration of the disease, scores of the Unified Parkinson's Disease Rating Scale and Hoehn and Yahr staging in PD patients. These values did not correlate with age in the control group. These results suggest that serum levels of zinc and copper do not play any role as risk factors for PD.
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PMID:Serum levels of zinc and copper in patients with Parkinson's disease. 146 36

A 12-year-old boy developed occasional attacks of oculogyric crisis after physical exercises or when tired. Following the initial symptom, progressive Parkinsonian features such as bradykinesia, muscular rigidity, hand tremors in posture, mild dysarthria and disorder of postural reflexes developed. There was no marked diurnal fluctuation o symptoms. Serum ceruloplasmin, copper levels, cranial X-ray CT scan and MRI were normal. Measurement of the plasma levels of L-dopa after single oral administration (300 mg) were normal. The treatment with L-dopa improved the Parkinsonian features excluding the attacks of oculogyric crisis in a few weeks. This case is not identical with juvenile Parkinsonism proposed by Yokochi et al for lack of both crural or truncal dystonia and remarkable response to L-dopa. Oculogyric crisis is known in several patients with severe generalized dystonia, and seldom in patients with Parkinson disease or juvenile Parkinsonism. Oculogyric crisis may be one of focal dystonias confined to extraocular muscles.
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PMID:[Oculogyric crisis as an initial symptom of juvenile parkinsonism-like disease]. 260 35

A 42-year-old man had suffered from Parkinson's disease for 5 years. Levodopa was effective, but the wearing-off phenomena were severe. Because of relatively low levels of serum copper and ceruloplasmin, D-penicillamine was administered. D-penicillamine increased plasma levodopa concentrations, thereby improving his parkinsonian symptoms. We propose that D-penicillamine facilitates levodopa absorption and, hence, the efficacy of the antiparkinsonian drug.
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PMID:Effect of D-penicillamine on pharmacokinetics of levodopa in Parkinson's disease. 822 5

A case of familial juvenile parkinsonism with dementia, orthostatic hypotension, neurogenic bladder and constipation was reported. He had been in a good health until the age of 28 when a finger tremor occurred on effort to hold hands in a definite position, and disturbances in gait and speech were noted. These symptoms were relieved by levodopa treatment followed by dyskinesia and motor fluctuations. Three years later, he complained of faintness, constipation and urinary frequency. The neurological examination revealed mentally sound male with masked face, tremor and rigidity in his extremities, and short step gait with lateropulsion. Urodynamic study showed uninhibited bladder. In the following years, orthostatic hypotension, dysuria and urinary retention developed gradually. He became mentally loose and was unable to take medicines appropriately. When in the Nishiojiya Byoin National Sanatorium, he tried to snake out the hospital many times. His parents and a brother suffered from Parkinson's disease and juvenile parkinsonism, respectively, suggesting an autosomal dominant inheritance. On admission to our hospital, he was apathetic. He had masked face, bilateral postural tremor, frozen gait and dyskinesia in the right lower extremity. Little bradykinesia or rigidity was noted. His muscle tone and deep tendon reflexes were decreased but neither muscular wasting, weakness, ataxia nor sensory disturbance was observed. Laboratory data including ceruloplasmin, copper, dopamine-beta-hydroxylase and lysosomal enzyme activities were normal except for mild anemia. A cranial CT scan revealed mild cortical atrophy in the frontal and temporal lobes, but nerve conduction study and cortical evoked potentials showed no abnormality. While in the hospital, his mental functions deteriorated to the state of dementia and orthostatic hypotension became apparent.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Familial juvenile parkinsonism with dementia and autonomic failure--a case report]. 833 79

Hallervorden-Spatz syndrome (HSS) (OMIM #234200) is a rare, autosomal recessive neurode-generative disorder with brain iron accumulation as a prominent finding. Clinical features include extrapyramidal dysfunction, onset in childhood, and a relentlessly progressive course. Histologic study reveals massive iron deposits in the basal ganglia. Systemic and cerebrospinal fluid iron levels are normal, as are plasma levels of ferritin, transferrin and ceruloplasmin. Conversely, in disorders of systemic iron overload, such as haemochromatosis, brain iron is not increased, which suggests that fundamental differences exist between brain and systemic iron metabolism and transport. In normal brain, non-haem iron accumulates regionally and is highest in basal ganglia. Pathologic brain iron accumulation is seen in common disorders, including Parkinson's disease, Alzheimer's disease and Huntington disease. In order to gain insight into normal and abnormal brain iron transport, metabolism and function, our approach was to map the gene for HSS. A primary genome scan was performed using samples from a large, consanguineous family (HS1) (see Fig. 1). While this family was immensely powerful for mapping, the region demonstrating homozygosity in all affected members spans only 4 cM, requiring very close markers in order to detect linkage. The HSS gene maps to an interval flanked by D20S906 and D20S116 on chromosome 20p12.3-p13. Linkage was confirmed in nine additional families of diverse ethnic backgrounds.
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PMID:Homozygosity mapping of Hallervorden-Spatz syndrome to chromosome 20p12.3-p13. 894 32

New findings on the role of LfR (lactotransferrin receptor), MTf (melanotransferrin), CP (ceruloplasmin) and DCT1 (Divalent Cation Transporter) in brain iron transport, obtained during the past 3 years, are important advances in the fields of physiology and pathophysiology of brain iron metabolism. According to these findings, disruption in the expression of these proteins in the brain is probably one of the important causes of the altered brain iron metabolism in age-related neurodegenerative diseases, including Parkinson's Disease, Alzheimer's disease, Huntington's disease and amyotrophic lateral sclerosis. Further studies on the involvement of LfR, MTf and DCT1 in iron uptake by and CP in iron egress from different types of brain cells as well as control mechanisms of expression of these proteins in the brain are critical for elucidating the causes of excessive accumulation of iron in the brain and neuronal death in neurodegenerative diseases.
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PMID:Expression of iron transport proteins and excessive iron accumulation in the brain in neurodegenerative disorders. 972 18

Recent evidence suggest the implication of transition metals leading to overproduction of free radicals as a possible causal factor in the death of nigral cells associated to Parkinson's disease (PD). Iron depots in the basal ganglia of PD patients have been described; in addition, contents of nigral copper have been found decreased, while its concentration in cerebrospinal fluid (CSF) is raised, particularly the free form of the metal. To search for a possible link between altered copper concentrations and PD, we advanced the hypothesis that ferroxidase activity of ceruloplasmin is decreased in the CSF of PD patients. We studied 35 untreated PD patients, 14 L-3,4-dihydroxyphenylalanine (L-DOPA)-treated PD patients and 26 controls. Both CSF ferroxidase activity and CSF copper content were measured and correlated with the clinical stage of the disease. We found that untreated PD patients had a significant reduction of 40% in CSF ferroxidase while CSF copper was slightly increased as compared with both the values in L-DOPA-treated PD patients and controls. We also found that the fraction of copper linked to ferroxidase in untreated PD is inversely related to the clinical stage of the disease.
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PMID:Reduced ferroxidase activity in the cerebrospinal fluid from patients with Parkinson's disease. 1032 54

In a previous study we found copper dyshomeostasis in patients with Alzheimer's disease. In this study, levels of copper in plasma, of ceruloplasmin in serum and ceruloplasmin oxidative activity as well as superoxide dismutase (SOD) activity in erythrocytes were determined in 40 patients with Parkinson's disease and their healthy age- and gender-matched controls. Copper concentrations did not differ significantly in the two groups, whereas both ceruloplasmin concentrations and ceruloplasmin oxidative activity were significantly lower in the patients, also relative to ceruloplasmin mass. SOD activity was not significantly different in the two groups but decreased significantly with the duration of disease. The same was found for ceruloplasmin oxidative activity. Ceruloplasmin oxidative activity and SOD activity did not decrease with age. Levels of serum iron, serum ferritin and total iron binding capacity were determined in about 30 of the patients and an equal number of controls and were not found to differ. Transferrin levels were significantly lower in the patients than in their controls but, conversely, the transferrin saturation was significantly higher in the patients. The results indicate that patients with Alzheimer's disease and Parkinson's disease have defective ceruloplasmin and SOD activities in common and that these defects are not necessarily associated with major disturbances in iron homeostasis.
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PMID:Copper, ceruloplasmin, superoxide dismutase and iron parameters in Parkinson's disease. 1060 87

In two previous studies we found copper dyshomeostasis in patients with Alzheimer's disease and in patients with Parkinson's disease. In this study, the levels of copper in plasma, of ceruloplasmin in serum, ceruloplasmin oxidative activity, ceruloplasmin specific oxidative activity (activity related to mass) as well as superoxide dismutase (SOD) activity in erythrocytes have been determined in 14 patients with amyotrophic lateral sclerosis and their healthy age- and gender-matched controls. Three of the patients had a familial form of the disease or were suspected of having it. The mean values of all parameters were found not to differ significantly between the patients and their controls (Student's t-test; P>0.05). By testing the equality of variances (F distribution) we found that the variances of individual results for ceruloplasmin specific oxidative activity and SOD activity differed significantly between the patients group and the controls group (P= 0.021 and P=0.003), but the individual results of these two activities were not correlated (P>0.05). We conclude that disturbances in ceruloplasmin specific oxidative activity and SOD activity could contribute to motor neurone death in amyotrophic lateral sclerosis, and since the two enzyme activities are not correlated it is uncertain which one is more closely related to the pathology of the disease.
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PMID:Copper, ceruloplasmin and superoxide dismutase (SOD) in amyotrophic lateral sclerosis. 1106 53

Wilson's disease (WD) patients often present with Parkinson's disease (PD). Furthermore, most patients with PD have reduced ceruloplasmin, a characteristic of Wilson's disease. WD is an autosomal recessive disease (requires two faulty copies of a gene to produce a homozygote individual) that afflicts 1 in 1000 people. However, the number of people with one faulty copy (heterozygotes) is much larger, probably about 2% of the population. I hypothesize that the large number of heterozygotes for WD are at greatly increased risk for idiopathic PD, because these people accumulate free copper in the basal ganglia at a slower rate than homozygotes, which accounts for the fact that PD usually develops after 40 years of age. In WD, a ceruloplasmin deficiency results in accumulation of free Cu in the liver, brain, kidneys, etc. The excess Cu results in impaired Zn absorption, which would account for the low levels of Zn in the brains of PD patients. Moreover, the high levels of Fe found in the substantia nigra of PD patients may perhaps be explained by free Cu binding to iron binding protein-1 (IBP-1), causing it to malfunction and preventing it from detaching itself from the transferrin receptor (TfR) inhibition gene, resulting in expression of TfR even when the cell has plenty of Fe. The gradual accumulation of Fe and Cu would explain the damage inflicted on the substantia nigra by free radicals catalyzed by these two metals and which is exacerbated by the low levels of CuZnSOD, due to the Zn deficiency mentioned above. Moreover, if this hypothesis is correct, then PD could be used to help discover the gene (or genes) responsible for WD and vice versa. Furthermore, idiopathic PD could be prevented by identifying the heterozygote individuals and providing them with Zn supplementation, Cu chelation therapy and phlebotomy to eliminate Fe.
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PMID:Is Parkinson's disease the heterozygote form of Wilson's disease: PD = 1/2 WD? 1142 82


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