Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cadmium and aluminium ions - especially in acid soils - are taken up by plants which then become poisoned by them. As a result the roots of the plants become deformed, and the green parts become chlorotic and underdeveloped. The yield will thus be sharply reduced. Culture fluid and culture pot experiments have shown that the toxic effects can be inhibited by magnesium. Investigations have proved that the inhibition is competitive and is based on the antagonism of cadmium and aluminium towards magnesium. Toxic cadmium and aluminium concentrations in the soil can be decreased by the use of non-acidifying fertilizers, and inhibited or prevented with fertilizers containing magnesium, eg Agronit (28% N and 2.5% Mg) or Kardonit (28% N and 5.5% Mg) (Borsod Chemical Works). Cadmium and aluminium taken up by plants are equally detrimental to animal and human organisms through the nutrition chain. For example cadmium may cause sterility, while aluminium may be implicated in Alzheimer's and Parkinson's disease. Magnesium moderates the effects of these two toxic elements in the human organism as well as in plants.
 ...
PMID:Magnesium inhibits the harmful effects on plants of some toxic elements. 186 32

The contents of indispensable major elements sodium (Na), phosphorus (P), calcium (Ca), magnesium (Mg), trace elements iron (Fe), copper (Cu), nickel (Ni), zinc (Zn), strontium (Sr), vanadium (V), chromium (Cr), manganese (Mn), molybdenum (Mo), and other elements lead (Pb), silicon (Si), aluminium (Al), titanium (Ti), barium (Ba), lanthanum (La), cadmium (Yb), cerium (Ce), scandium (Sc), silver (Ag), in cerebrospinal fluid (CSF) were measured in 13 patients suffering from Parkinson disease before and after autotransplantation of adrenal medulla. It was found that while the patients' objective symptoms were relieved and the contents of monoamine transmitters were changed, the contents of P, V, Co, Cr, in CSF increased significantly (P less than 0.05 or 0.01) at the first, 2nd, 4th, 6th, and 8th week, the contents of Mn in CSF also increased significantly at the first 4th week (P less than 0.05) but decreased significantly at the 8th week the contents of Zn in CSF increased significantly (P less than 0.05) at the 2nd week; Mo increased significantly (P less than 0.05 or 0.01) at the 4th and 8th week B increased significantly (P less than 0.05) at the first week; the contents of Ca, Na, Sr, Ba, Al, Ti, La, Ce, Yb, Sc, Ag in CSF increased significantly (P less than 0.05 or 0.01) at the 8th week, Mg, Fe, Cu Ni, Pb, Si, Cd remained unchanged after operation. The results suggest that the contents of these chemical elements can be affected by this kind of operation, indicating that these elements are involved in the pathogenesis of Parkinsonism.
 ...
PMID:[Determination of multiple chemical elements in CSF in Parkinson disease after intracerebral autotransplantation of the adrenal medulla]. 186 88

It has been suggested that nitric oxide could be implicated in the neuronal degeneration of substantia nigra compacta in patients with Parkinson's disease. Recently, it has been reported decreased CSF nitrate levels (oxidation product that provides an indirect estimation of nitric oxide) in Parkinson's disease patients, assessed with a colorimetric method. We studied the CSF and plasma levels of nitrate with a kinetic cadmium-reduction method in 31 Parkinson's disease patients and 38 matched controls. The CSF and plasma nitrate levels were not correlated either in patient or in the control group, and they did not differ significantly between the two study groups. They were not influenced significantly by antiparkinsonian drugs in patients, although there was a trend for CSF nitrate levels to be higher in patients treated with levodopa or with dopamine agonists. CSF and plasma nitrate levels did not correlate with age at onset, duration, scores of the unified Parkinson's disease rating scales and Hoehn & Yahr staging in the patients group. These date suggest that CSF and plasma levels of nitrate are apparently unrelated with the risk for PD.
 ...
PMID:Cerebrospinal fluid nitrate levels in patients with Parkinson's disease. 874 Nov 30

Alpha-synuclein filaments are the major component of intracytoplasmic inclusion bodies characteristic of Parkinson's disease and related disorders. The process of alpha-synuclein filament formation proceeds via intermediate or protofibrillar species, each of which may be cytotoxic. Because high levels of calcium(II) and other metal ions may play a role in disease pathogenesis, we investigated the influence of calcium and other metals on alpha-synuclein speciation. Here we report that calcium(II) and cobalt(II) selectively induce the rapid formation of discrete annular alpha-synuclein oligomeric species. We used atomic force microscopy to monitor the aggregation state of alpha-synuclein after 1 d at 4 degrees C in the presence of a range of metal ions compared with the filament formation pathway in the absence of metal ions. Three classes of effect were observed with different groups of metal ions: (1) Copper(II), iron(III), and nickel(II) yielded 0.8-4 nm spherical particles, similar to alpha-synuclein incubated without metal ions; (2) magnesium(II), cadmium(II), and zinc(II) gave larger, 5-8 nm spherical oligomers; and, (3) cobalt(II) and calcium(II) gave frequent annular oligomers, 70-90 nm in diameter with calcium(II) and 22-30 nm in diameter with cobalt(II). In the absence of metal ions, annular oligomers ranging 45-90 nm in diameter were observed after 10 d incubation, short branched structures appeared after a further 3 wk and extended filaments after 2-3 mo. Previous studies have shown that alpha-synuclein calcium binding is mediated by the acidic C terminus. We found that truncated alpha-synuclein (1-125), lacking the C-terminal 15 amino acids, did not form annular oligomers upon calcium addition, indicating the involvement of the calcium-binding domain.
 ...
PMID:Calcium(II) selectively induces alpha-synuclein annular oligomers via interaction with the C-terminal domain. 1553 54

The aggregation of alpha-synuclein in the dopaminergic neurons of the substantia nigra is a critical step in the Parkinson's disease (PD). The etiology of the disease is unknown but recent epidemiological and experimental studies have renewed interest in the hypothesis that environmental factors, especially herbicides and metals, have a role on the pathogenesis of PD. For the first time, the association constants of alpha-synuclein with five herbicides have been calculated using a capillary electrophoresis (CE) method. In addition, the effect of a number of metals on this binding has been investigated. It appears that the herbicides preferentially bind to a partially folded intermediate conformation of alpha-synuclein induced by manganese, aluminium, cadmium, copper and zinc. Then, metal increases the synuclein-herbicide association. However, this study shows contrasting actions with the antibiotic rifampicin and magnesium addition leading to a decrease of the alpha-synuclein-herbicide interaction even if other metals are present in the bulk solvent. Considering epidemiological studies, all these results suggest an underlying molecular basis for PD and related body diseases.
 ...
PMID:Effect of metals on herbicides-alpha-synuclein association: a possible factor in neurodegenerative disease studied by capillary electrophoresis. 1614 78

Plateau potentials can be elicited in nigral GABAergic neurons by injection of 500 ms depolarizing current pulses from hyperpolarized holding potentials in whole-cell recordings in vitro. In approximately one-third of these neurons, plateau potentials were observed under control conditions and could be elicited in the remaining neurons after blocking potassium conductances. Application of the L-type calcium channel agonist Bay K 8644 or activation of NMDA receptors enhanced plateau potentials observed under control conditions and caused a plateau to be elicited in neurons not exhibiting it previously. The plateau potential was abolished in calcium-free buffer, as well as by nickel or cadmium. The L-type calcium channel blockers nimodipine and nifedipine abolished the plateau potential observed under control conditions but did not affect plateaus unmasked by tetraethylammonium. Plateau potentials observed under control conditions as well as those observed in the presence of Bay K 8644, NMDA, or tetraethylammonium were abolished in low-sodium buffer and by the calcium-activated nonselective cation conductance blocker flufenamic acid. These data suggest that nigral plateau potentials are mediated by a calcium-activated nonselective cation conductance (I(CAN)) that is activated by calcium entry predominantly through L-type calcium channels. In many nigral neurons, I(CAN) is masked by tetraethylammonium-sensitive potassium conductances, but plateaus can be evoked after increasing calcium conductances. The I(CAN)-mediated plateau potential in nigral GABAergic neurons likely affects the way these neurons integrate input and may represent a mechanism contributing to the rhythmic firing of these neurons seen in pathological conditions such as Parkinson's disease.
 ...
PMID:A calcium-activated nonselective cation conductance underlies the plateau potential in rat substantia nigra GABAergic neurons. 1756 14

In the present study, we investigated the effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on lipoamide dehydrogenase activity and metallothionein content. Lipoamide dehydrogenase is a flavoprotein enzyme, which reduces lipoamide and low molecular weight thiols. This enzyme has also been involved in the conversion of ubiquinone (coenzyme Q-10, oxidized form) to ubiquinol (reduced form). Lipoamide dehydrogenase activity was measured spectrophotometrically following its incubation with different doses of MPTP, MPP+, and divalent metals. MPTP at higher concentrations inhibited the lipoamide dehydrogenase activity, whereas it's potent toxic metabolite 1-methyl-4-phenylpyridinium (MPP+) had a similar effect at lower concentration. Calcium and copper did not affect the enzyme activity at any of the doses tested, whereas, zinc dose dependently enhanced the lipoamide dehydrogenase activity. Additionally, levels of metallothionein in the mouse nigrostriatal system were measured by cadmium affinity method following administration of MPTP. Metallothionein content was significantly reduced in the substantia nigra (SN), and not in the nucleus caudatus putamen (NCP) following a single administration of MPTP (30 mg/kg, i.p.). Our results suggests that both lipoamide dehydrogenase activity and metallothionein levels may be critical for dopaminergic neuronal survival in Parkinson's disease and provides further insights into the neurotoxic mechanisms involved in MPTP-induced neurotoxicity.
 ...
PMID:Role of lipoamide dehydrogenase and metallothionein on 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine-induced neurotoxicity. 1776 76

Epidemiological evidence suggests that pesticides and other environmental exposures may have a role in the etiology of idiopathic Parkinson's disease (PD). However, there is little human data on risk associated with specific pesticide products, including organic pesticides such as rotenone with PD. Using a case-control design, this study examined self-reports of exposure to pesticide products, organic pesticides such as rotenone, and other occupational and environmental exposures on the risk of PD in an East Texas population. The findings demonstrated significantly increased risk of PD with use of organic pesticides such as rotenone in the past year in gardening (OR = 10.9; 95% CI = 2.5-48.0) and any rotenone use in the past (OR = 10.0; 95% CI = 2.9-34.3). Use of chlorpyrifos products (OR = 2.0; 95% CI = 1.02-3.8), past work in an electronics plant (OR = 5.1; 95% CI = 1.1-23.6), and exposure to fluorides (OR = 3.3; 95% CI = 1.03-10.3) were also associated with significantly increased risk. A trend of increased PD risk was observed with work history in paper/lumber mill (OR = 6.35; 95% CI = 0.7-51.8), exposure to cadmium (OR = 5.3; 95% CI = 0.6-44.9), exposure to paraquat (OR = 3.5; 95% CI = 0.4-31.6), and insecticide applications to farm animals/animal areas and agricultural processes (OR = 4.4; 95% CI = 0.5-38.1). Cigarette smoking, alcohol use, and fish intake were associated with reduced risk. In summary, this study demonstrates an increased risk of PD associated with organic pesticides such as rotenone and certain other pesticides and environmental exposures in this population.
 ...
PMID:Pesticide/environmental exposures and Parkinson's disease in East Texas. 1904 91

Improved living conditions have led to a steady increase in the life expectancy of humans in most countries. However, this is accompanied by an increased probability of suffering from neurodegenerative diseases like Alzheimer's disease or Parkinson's disease. Unfortunately, the therapeutic possibilities for curing these diseases are very limited up to now. Many studies indicate that a variety of environmental factors contribute to the initiation and promotion of neurodegenerative diseases. For example, the role of metal exposure and disturbance of metal homeostasis in the brain is discussed in this respect. However, most studies focus on the neurological and toxicological aspects but not on a detailed characterisation of the species of the involved metals. Therefore, this review summarizes the neurotoxic effects of selected metals on humans and focuses on contributions from trace element speciation analysis with relevance to neuroscientific research. In spite of the advance in instrumentation and methodology of speciation analysis there are few applications for matrices like cerebrospinal fluid which is due to limited access to these samples and analytical challenges caused by matrix interferences, low concentrations and limited stability of many trace element species of interest. The most relevant neurotoxic metals aluminium, lead, manganese and mercury are reviewed in detail while further metals like cadmium, arsenic, bismuth and tin are briefly discussed. Current results indicate that knowledge on trace element speciation can contribute to a better understanding of the transport of metals across the neural barriers and potentially of their role in diseased human brains.
 ...
PMID:JEM spotlight: metal speciation related to neurotoxicity in humans. 1943 51

Environmental and occupational exposures to heavy metals such as methylmercury (MeHg) and cadmium (Cd) pose significant health risks to humans, including neurotoxicity. The underlying mechanisms of their toxicity, however, remain to be fully characterized. Our previous studies with Cd and MeHg have demonstrated that the perturbation of the ubiquitin-proteasome system (UPS) was associated with metal-induced cytotoxicity and apoptosis. We conducted a microarray-based gene expression analysis to compare metal-altered gene expression patterns with a classical proteasome inhibitor, MG132 (0.5 microM), to determine whether the disruption of the UPS is a critical mechanism of metal-induced toxicity. We treated mouse embryonic fibroblast cells at doses of MeHg (2.5 microM) and Cd (5.0 microM) for 24 h. The doses selected were based on the neutral red-based cell viability assay where initial statistically significant decreases in variability were detected. Following normalization of the array data, we employed multilevel analysis tools to explore the data, including group comparisons, cluster analysis, gene annotations analysis (gene ontology analysis), and pathway analysis using GenMAPP and Ingenuity Pathway Analysis (IPA). Using these integrated approaches, we identified significant gene expression changes across treatments within the UPS (Uchl1 and Ube2c), antioxidant and phase II enzymes (Gsta2, Gsta4, and Noq1), and genes involved in cell cycle regulation pathways (ccnb1, cdc2a, and cdc25c). Furthermore, pathway analysis revealed significant alterations in genes implicated in Parkinson's disease pathogenesis following metal exposure. This study suggests that these pathways play a critical role in the development of adverse effects associated with metal exposures.
 ...
PMID:A system-based comparison of gene expression reveals alterations in oxidative stress, disruption of ubiquitin-proteasome system and altered cell cycle regulation after exposure to cadmium and methylmercury in mouse embryonic fibroblast. 2006 41


1 2 3 4 Next >>