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)

In more than 90% of patients with idiopathic Parkinson's disease (PD) hyperechogenicity of the substantia nigra (SN) can be found by transcranial sonography (TCS) as a typical, stable sign. Animal experiments provided first evidence that SN hyperechogenicity may be associated with increased tissue iron levels. Two consecutive studies revealed the same association in human brain. Postmortem brains of 60 subjects without clinical signs for Parkinson's disease during life time at different ages were scanned by ultrasound with planimetric measurement of the echogenic area of the SN. Afterwards the SN was dissected and used for histological examination and determination of iron content in all brains as well as ferritin and neuromelanin content in 40 brains. A significant positive correlation was found between the echogenic area of the SN and the concentration of iron, H- and L-ferritins. A multivariate analysis performed considering the iron content showed a significant negative correlation between echogenicity and neuromelanin content of the SN. Iron staining confirmed the biochemical findings. In PD a typical loss of neuromelanin and increase of iron is observed in this brain area. However, it is not clear yet, whether iron accumulation is a primary cause or a secondary phenomenon in the disease process. Screening of genes involved in brain iron metabolism showed a significant association of some sequence variations of the ceruloplasmin gene with PD. Others were associated with the ultrasound marker for increased iron levels in both PD patients and control subjects. As SN hyperechogenicity is typical for PD or subjects with a preclinical impairment of the nigrostriatal system, these findings indicate that TCS enables the detection of increased iron and decreased neuromelanin levels at the SN, even before the clinical manifestation of PD.
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PMID:In vivo detection of iron and neuromelanin by transcranial sonography--a new approach for early detection of substantia nigra damage. 1675 82

The understanding of oxidative damage in different neurodegenerative diseases could enhance therapeutic strategies. Our objective was to quantify lipoperoxidation and other oxidative products as well as the activity of antioxidant enzymes and cofactors in cerebrospinal fluid (CSF) samples. We recorded data from all new patients with a diagnosis of either one of the four most frequent neurodegenerative diseases: Parkinson's disease (PD), Alzheimer's disease (AD), Huntington's disease (HD) and lateral amyotrophic sclerosis (ALS). The sum of nitrites and nitrates as end products of nitric oxide (NO) were increased in the four degenerative diseases and fluorescent lipoperoxidation products in three (excepting ALS). A decreased Cu/Zn-dependent superoxide dismutase (SOD) activity characterized the four diseases. A significantly decreased ferroxidase activity was found in PD, HD and AD, agreeing with findings of iron deposition in these entities, while free copper was found to be increased in CSF and appeared to be a good biomarker of PD.
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PMID:Free copper, ferroxidase and SOD1 activities, lipid peroxidation and NO(x) content in the CSF. A different marker profile in four neurodegenerative diseases. 1830 39

Numerous recent findings indicate the involvement of a neuroinflammatory reaction in the neurodegeneration in idiopathic Parkinson's disease (PD). We examined 29 consecutive patients with PD, ages 54-84 years, most of whom were moderately impaired (median UPDRS 19; Hoehn-Yahr 3; MMSE 28). A series of serum biomarkers were investigated, and their levels were correlated with the degree of the motor and cognitive impairment. There were no abnormalities of IL-6, acute phase proteins (C-reactive protein, serum amyloid A, alpha 1-antitrypsin, orosomucoid, ceruloplasmin, alpha 2-macroglobulin, transferrin, prealbumin) and factors of the complement system (C1q, C1-INH, C3, C4). A decrease in Mannan-binding lectin (MBL) levels was observed in six patients; an elevation of tumor necrosis factor-alpha (TNF-alpha) was found in 12 patients. No statistically significant correlation was found between the patient's clinical state (neuropsychologic and motor, as expressed by UPDRS III, Hoehn-Yahr, and MMSE) and the immunomarker changes. Our results indicate that the inflammatory process may be reflected in the serum; nevertheless, further research is needed to elucidate the possible clinical implications.
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PMID:Serum inflammatory biomarkers in Parkinson's disease. 1867 91

Ceruloplasmin (Cp) is the strongest ferroxidase in human plasma. Hereditary deficiency of this protein, named aceruloplasminemia, is an interesting model to elucidate the pathogenesis and pathophysiology of neurodegeneration induced by oxidative stress. Enhanced oxidative stress due to excessive iron accumulation is observed in the brains of aceruloplasminemia patients. Rotenone, a selective mitochondrial complex I inhibitor, induces neurodegeneration mimicking Parkinson's disease. We investigated the influence of Cp deficiency upon neurodegeneration using rotenone-treated, Cp-deficient mouse brains. Immunohistochemical examination showed that acrolein, one of the products of lipid peroxides, and ubiquitin were more markedly immunoreacted in the brains of rotenone-treated, Cp-deficient mice than in rotenone-untreated, Cp-deficient or rotenone-treated, wild-type mice. These molecules were localized in neuronal cells. These results suggested that rotenone-induced lipid peroxidation and accumulation of ubiquitin immunoreactivity were enhanced in the absence of Cp. Therefore, Cp may protect neuronal cells from oxidative stress-induced neurodegeneration.
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PMID:Increased vulnerability to rotenone-induced neurotoxicity in ceruloplasmin-deficient mice. 1880 45

Ceruloplasmin functions as a ferroxidase in iron metabolism. Parkinson's disease (PD) is characterized by an increase in brain iron. We postulated that lower circulating ceruloplasmin levels in PD would result in rapid brain iron accumulation and an earlier age of onset. Consecutive PD patients were separated into subgroups with younger (< or = 60 years, n = 62) and older ages of onset (> 60, n = 29), and compared to non-PD controls (n = 40). A one-way ANOVA comparing ceruloplasmin levels showed a very robust effect [F(2,128) = 46.4, p < 1e-99]. Post hoc analysis demonstrated that the younger-onset PD subgroup [22.0 mg/dl +/- 6.5 SD] had a lower mean ceruloplasmin level compared to the older-onset PD subgroup [35.7 +/- 10.4] and controls [35.6 +/- 8.4], whose levels did not differ from each other. Ceruloplasmin levels showed robust correlation with age of onset in all 91 PD patients [r = 0.56, r(2) = 0.31, p < 0.0001] but not in the non-PD controls [r = 0.16, r(2) = 0.03, not significant]. Mode of onset and duration of PD showed no relationship to ceruloplasmin. Serum copper and ferritin, available in most patients, did not differ between the PD subgroups. Younger-onset PD patients have significantly lower levels of serum ceruloplasmin compared to those with older-onset PD. Ceruloplasmin may play a role in the etiopathogenesis of younger-onset PD patients and merits further study.
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PMID:Lower serum ceruloplasmin levels correlate with younger age of onset in Parkinson's disease. 1915 62

The concentration of plasma copper, ceruloplasmin (CRP), non-ceruloplasmin-bound Cu (NCBC), and metallothioneins (MTs) were studied as putative biomarkers for neurodegenerative diseases in patients and in their first-degree relatives. We found increased levels of Cu in the plasma of Alzheimer's disease (AD), Parkinson's disease (PD), and vascular dementia (VD) patients, and the increase observed in VD group was linked to the evolution of the disease. CRP was also elevated in response to the inflammatory component of the diseases, however, a correlation with illness progression was only observed in VD patients. The level of MTs is proportional to the evolution of VD. The Cu/CRP and Cu/MTs ratios are both indicative of disease progression for AD patients but not for those with PD or VD. Moreover, there is a correlation between the NCBC levels and the cognitive impairment estimated through the Mini-mental State Examination (MMSE) scale. This dependence is linear for AD and PD patients and non-linear for the VD ones. The relative values of NCBC showed dependence on the disease duration, especially for AD. Copper measurement and the Cu/CRP ratio may be predictive markers of risk for the first-degree relatives of AD patients. We believe that these results are valuable as a reliable clinical tool.
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PMID:Clinical utility of copper, ceruloplasmin, and metallothionein plasma determinations in human neurodegenerative patients and their first-degree relatives. 2002 14

Neurodegeneration with brain iron accumulation (NBIA) is etiologically, clinically, and by imaging a heterogeneous group including NBIA types 1 [pantothenate kinase-associated neurodegeneration (PKAN)] and 2 (PLA2G6-associated neurodegeneration), neuroferritinopathy, and aceruloplasminaemia. Data on genetically defined Indian-subcontinent NBIA cases are limited. We report 6 patients from the Indian-subcontinent with a movement disorder and MRI basal ganglia iron deposition, compatible with diagnosis of an NBIA syndrome. All patients were screened for abnormalities in serum ceruloplasmin and ferritin levels and mutations in NBIA-associated genes [pantothenate kinase 2 (PANK2), PLA2G6 and ferritin light chain (exon 4)]. We present clinical, imaging and genetic data correlating phenotype-genotype relations. Four patients carried PANK2 mutations, two of these were novel. The clinical phenotype was mainly dystonic with generalized dystonia and marked orobulbar features in the 4 adolescent-onset cases. One of the four had a late-onset (age 37) unilateral jerky postural tremor. His mutation, c.1379C>T, appears associated with a milder phenotype. Interestingly, he developed the eye-of-the-tiger sign only 10 years after onset. Two of the six presented with adult-onset levodopa (L-dopa)-responsive asymmetric re-emergent rest tremor, developing L-dopa-induced dyskinesias, and good benefit to deep brain stimulation (in one), thus resembling Parkinson's disease (PD). Both had an eye-of-the-tiger sign on MRI but were negative for known NBIA-associated genes, suggesting the existence of further genetic or sporadic forms of NBIA syndromes. In conclusion, genetically determined NBIA cases from the Indian subcontinent suggest presence of unusual phenotypes of PANK2 and novel mutations. The phenotype of NBIA of unknown cause includes a PD-like presentation.
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PMID:Indian-subcontinent NBIA: unusual phenotypes, novel PANK2 mutations, and undetermined genetic forms. 2062 44

This short review describes a series of case-control studies on the concentration and oxidative activity of ceruloplasmin (CP) in serum and the activity of superoxide dismutase (SOD1) in erythrocytes in patients with Alzheimer's disease (AD), Parkinson's disease (PD) and Down's syndrome (DS). The same parameters were re-examined in the PD patients 5 years later. The specific oxidative activity (oxidative activity related to mass) of CP was calculated in PD and DS. In AD and PD the oxidative activity of CP and SOD1 activity was significantly lower in patients than controls. The specific oxidative activity of CP was also significantly lower in PD patients. The difference in all parameters determined was still present 5 years later in PD patients. There was no difference in the concentration or activity of CP in patients with DS and controls. Because of the gene-dose effect (the gene for SOD1 is located on chromosome 21); the SOD1 activity was 50% higher in the patients than the controls. The CP specific oxidative activity and SOD1 activity were found to be significantly lower in the older (>40 years) than the younger DS patients. Whether changes in CP and SOD1 in AD, PD and DS are primary changes or a result of prolonged disease burden needs to be examined.
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PMID:Case-control studies on ceruloplasmin and superoxide dismutase (SOD1) in neurodegenerative diseases: a short review. 2085 26

The capacity to act as an electron donor and acceptor makes iron an essential cofactor of many vital processes. Its balance in the body has to be tightly regulated since its excess can be harmful by favouring oxidative damage, while its deficiency can impair fundamental activities like erythropoiesis. In the brain, an accumulation of iron or an increase in its availability has been associated with the development and/or progression of different degenerative processes, including Parkinson's disease, while iron paucity seems to be associated with cognitive deficits, motor dysfunction, and restless legs syndrome. In the search of DNA sequence variations affecting the individual predisposition to develop movement disorders, we scanned by DHPLC the exons and intronic boundary regions of ceruloplasmin, iron regulatory protein 2, hemopexin, hepcidin and hemojuvelin genes in cohorts of subjects affected by Parkinson's disease and idiopathic neurodegeneration with brain iron accumulation (NBIA). Both novel and known sequence variations were identified in most of the genes, but none of them seemed to be significantly associated to the movement diseases of interest.
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PMID:Analysis of nucleotide variations in genes of iron management in patients of Parkinson's disease and other movement disorders. 2098 Dec 30

In vivo and post-mortem studies have demonstrated that increased nigral iron content in patients with Parkinson's disease is a prominent pathophysiological feature. However, the mechanism and risk factors associated with nigral iron deposition in patients with Parkinson's disease have not been identified and represent a key challenge in understanding its pathogenesis and for its diagnosis. In this study, we assessed iron levels in patients with Parkinson's disease and in age- and gender-matched control subjects by measuring phase values using magnetic resonance based susceptibility-weighted phase imaging in a 3T magnetic resonance system. Phase values were measured from brain regions including bilateral substantia nigra, globus pallidus, putamen, caudate, thalamus, red nucleus and frontal white matter of 45 patients with Parkinson's disease with decreased or normal serum ceruloplasmin levels, together with age- and gender-matched control subjects. Correlative analyses between phase values, serum ceruloplasmin levels and disease severity showed that the nigral bilateral average phase values in patients with Parkinson's disease were significantly lower than in control subjects and correlated with disease severity according to the Hoehn and Yahr Scale. The Unified Parkinson's Disease Rating Scale motor scores from the clinically most affected side were significantly correlated with the phase values of the contralateral substantia nigra. Furthermore, nigral bilateral average phase values correlated highly with the level of serum ceruloplasmin. Specifically, in the subset of patients with Parkinson's disease exhibiting reduced levels of serum ceruloplasmin, we found lowered nigral bilateral average phase values, suggesting increased nigral iron content, while those patients with normal levels of serum ceruloplasmin exhibited no changes as compared with control subjects. These findings suggest that decreased levels of serum ceruloplasmin may specifically exacerbate nigral iron deposition in patients with Parkinson's disease. Combining susceptibility-weighted phase imaging with serum ceruloplasmin determination is likely to be useful for the diagnosis and assessment of a subset of patients with Parkinson's disease.
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PMID:Decreased serum ceruloplasmin levels characteristically aggravate nigral iron deposition in Parkinson's disease. 2110 2


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