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)

This paper reviews the brain protective effect and mechanism of Polygonum multiflorum (PM), its extracts and active component, tetrahydroxystilbene-glucoside (2,3,5,4'-tetrahydroxystilbene-2-O-beta-D-glucoside) published in recent decade. They have major effects as calcium channel antagonists, antioxidant, cholinomimetic drugs and cholinesterase inhibitors, as well as actions in regulating cell apoptosis and prolonging the ageing. The brain protective mechanism of PM is multi-target, multi-link and multi-way. Therefore, PM has great applicative value in prevention and treatment of senile neuropathies, such as Alzheimer's disease, Parkinson's disease and vascular dementia, etc.
 ...
PMID:[Progress of study on brain protective effect and mechanism of Polygonum multiflorum]. 1631 26

Nicotinic acetylcholine receptors mediate the parasympathetic autonomic control of cardiac function. Aim of this study was the assessment of cardiac nicotinic acetylcholine receptor distribution with a novel (alpha4beta2) nicotinic acetylcholine receptor PET ligand (2-deoxy-2- [18F]fluoro-D-glucose-A85380) in humans. Five healthy volunteers without cardiac disease and six patients with either Parkinson's disease or multiple system atrophy without additional overt cardiac disease were evaluated with 2-deoxy-2-[18F]fluoro-D-glucose-A85380 PET-imaging to assess the cardiac parasympathetic innervation and the putative impact of both disorders. 2-deoxy-2- [18F]fluoro-D-glucose-A85380 whole body PET-scans were performed on a Siemens PET/CT biograph(TM) 75.4 min +/- 6.7 after i.v. injection of 371.2 +/- 58.1 MBq. Average count rate density of left ventricle ROI's and a standard ROI in the right lung were measured within three consecutive slices of 10.0 mm thickness. Heart-to-lung ratios were calculated in each volunteer and patient. Tracer uptake in the left ventricle could be measured in all of the five volunteers and the six patients. Heart-to-lung ratios in the volunteer group were not different from patients suffering from Parkinson's disease or MSA (3.2 +/- 0.5 vs 3.2 +/- 0.8 and 2.96+/-0.7, mean +/- SD), respectively. Human cardiac nicotinic acetylcholine receptors can be visualized and measured by 2-deoxy-2- [18F]fluoro-D-glucose-A85380 PET scans both in cardiac-healthy subjects and patients suffering from Parkinson's disease or multiple system atrophy. The heart- as well as the lung-tracer uptake was almost constant throughout all subjects leading to a good target-to-background ratio. These first results suggest no impact of either PD or MSA on cardiac nicotinic acetylcholine receptors.
 ...
PMID:Feasibility of 2-deoxy-2-[18F]fluoro-D-glucose- A85380-PET for imaging of human cardiac nicotinic acetylcholine receptors in vivo. 1659 19

1-Methyl-4-phenylpyridinium (MPP+) is a well-known neurotoxin which causes a clinical syndrome similar to Parkinson's disease. The classical mechanism of MPP+ toxicity involves its entry into cells through the dopamine transporter (DAT) to inhibit aerobic glucose metabolism, while recent studies suggest that an oxidative mechanism may contribute to the toxicity of MPP+. However, it has not been adequately determined what role these two mechanisms play in the development of neurotoxicity after MPP+ loading in the brain. To clarify this issue, MPP+ was added directly to fresh rat brain slices and the dynamic changes in the cerebral glucose metabolic rate (CMRglc) produced by MPP+ were serially and two-dimensionally measured using the dynamic positron autoradiography technique with [(18)F]2-fluoro-2-deoxy-D-glucose as a tracer. MPP+ dose-dependently increased CMRglc in each of the brain regions examined, reflecting enhanced glycolysis compensating for the decrease in aerobic metabolism. Treatment with DAT inhibitor GBR 12909 significantly attenuated the enhanced glycolysis induced by 10 microM MPP+ in the striatum. Treatment with free radical spin trap alpha-phenyl-N-tert-butylnitrone (PBN) significantly attenuated the enhancement of glycolysis induced by 100 microM MPP+ in all brain regions. These results suggest that the mechanism of the toxicity of MPP+ is biphasic and consists of a DAT-mediated mechanism selective for dopaminergic regions at a lower concentration of MPP+ (10 microM), and an oxidative mechanism that occurs at a higher concentration of MPP+ (100 microM) and is not restricted to dopaminergic regions.
 ...
PMID:Biphasic mechanism of the toxicity induced by 1-methyl-4-phenylpyridinium ion (MPP+) as revealed by dynamic changes in glucose metabolism in rat brain slices. 1739 68

Pathological conditions, such as Parkinson's disease and attention deficit hyperactivity disorder, have been linked to alterations of specific dopamine (DA) pathways. However, since exogenous DA does not cross the blood-brain barrier, DA levels can be modulated e.g. by DA precursors or DA reuptake blockers. Hereby histochemical, analytical and behavioral evidence shows that a galactosylated form of DA (GAL-DA) carries DA into the brain, thus modulating activity and nonselective attention in rats. To this aim adult male rats of the Naples high-excitability (NHE) and random bred controls (NRB) lines were given a single i.p. injection of GAL-DA (10 or 100 mg/kg). Three hours later the behavior was videotaped and analyzed for horizontal activity, orienting frequency and scanning duration. The dose of 100 mglkg of GAL-DA reduced by 25% the horizontal activity in NHE rats, mainly in the first part of the testing period. No effect was observed on orienting frequency or on scanning duration. However, GAL-DA 100 mg/kg was associated with longer rearing episodes in the second part of the testing period in NHE rats. In parallel experiments histochemistry with a galactose-specific lectin showed 10% increase in galactose residues into the striatum between 0.5 and 3.0 h. To quantify the level of GAL-DA, its metabolite DA-succinate and DA in the prefrontal cortex, neostriatum, and cerebellum, rats were killed 2.0 h after the injection of prodrug. Mass high performance liquid chromatography (HPLC) was used for analysis of GAL-DA and DA succinate whereas electrochemical HPLC for DA. Both HPLC techniques demonstrate that GAL-DA carries and releases DA into the brain. Specifically 100 mg/kg of GAL-DA increased DA level in the striatum in the NHE rats only. Moreover, DA in the mesencephalon (MES) was correlated positively with striatal and prefrontal cortex DA in NHE rats. In contrast DA in the MES was negatively correlated with striatal DA in NRB. GAL-DA disrupted these correlations in both rat lines. Thus, this new DA prodrug may modify DA neurotransmission and might have a potential clinical application.
 ...
PMID:Galactosylated dopamine enters into the brain, blocks the mesocorticolimbic system and modulates activity and scanning time in Naples high excitability rats. 1816 52

The neuroprotective effects of catalpol, an iridoid glycoside isolated from the fresh rehmannia roots, on the behavior and brain energy metabolism in senescent mice induced by d-galactose were assessed. Except control group, mice were subcutaneously injected with d-galactose (150 mg/kg body weight) for 6 weeks. From the fifth week, drug group mice were treated with catalpol (2.5, 5, 10 mg/kg body weight) and piracetam (300 mg/kg body weight) for the last 2 weeks. Behavioral changes including open field test and passive avoidance were examined after drug administration. To determine the brain damage, pathological alterations were measured by hematoxylin and eosin (HE) staining. The activities of lactate dehydrogenase (LDH), glutathione S-transferase (GSH-ST), glutamine synthetase (GS), creatine kinase (CK) in brain cortex and hippocampus were determined using different biochemical methods. Consistent with the cognition deficits, the activities of GSH-ST, GS and CK decreased while the activity of LDH increased in aging mice brain. Administration of catalpol for 2-weeks not only ameliorated cognition deficit, but also reversed the biochemical markers mentioned above and reduced the histological lesions in mouse brain. These results suggest that catalpol has protective effects on memory damage and energy metabolism failure in aging model mice and is worth testing for further preclinical study aimed for senescence or neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD).
 ...
PMID:d-galactose administration induces memory loss and energy metabolism disturbance in mice: protective effects of catalpol. 1857 5

Catalpol, an iridoid glucoside, separated from the root of Rehmannia glutinosa Libosch, has been known to show various neuroprotective effects. In humans and rodents, MPTP is well known to produce clinical, biochemical and neurochemical changes similar to those which occur in Parkinson's disease (PD). Furthermore, the accumulated evidence suggests that MPP(+), conversed by monoamine oxidase type B (MAO-B) in astrocytes principally, is the active metabolite of MPTP and the major cause to PD associated with mitochondrial dysfunction. In this study, we treated mesencephalic neuron-astrocyte and astrocytes cultures with MPTP (0.05 mM) respectively to investigate the neuroprotective effects of catalpol and the underlying protective mechanisms. Our results showed that pre-treatment with catalpol (0.5mM) for 1h prior to MPTP treatment attenuated mitochondrial dysfunction not only by reversing the activity of mitochondrial complex I, mitochondrial membrane potential (MMP), intracellular Ca(2+) level, and ROS accumulation as well as mitochondrial permeability transition (MPT) pore opening in mesencephalic neuron-astrocyte cultures, but also inhibiting MAO-B activity to protect neurons from more MPP(+) toxicity produced in astrocytes. Together, all of these indicated that catalpol possesses potent neuroprotective activity and may be a potential anti-PD drug worthy for further study.
 ...
PMID:Catalpol protects mesencephalic neurons against MPTP induced neurotoxicity via attenuation of mitochondrial dysfunction and MAO-B activity. 1884 May 19

This study investigated the proteomic changes at different time points in the precipitated pellets of rat spinal cords after applying complete spinal cord transection. By two-dimensional electrophoresis, matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectrometry, MALDI-TOF/TOF and peptide mass fingerprinting analysis, 44 proteins were identified, most of which are membrane and/or organellar proteins. They are mainly involved in metabolic processes (75%), developmental processes (30%), or responses to stimuli (30%), playing negative or positive roles. In particular, decreases of pyruvate dehydrogenase beta, aconitase 2, fumarate hydratase 1, and ATP synthase subunit 6 can lead to ATP depletion by crippling tricarboxylic acid cycle and oxidative phosphorylation. Decreases of several antioxidant proteins such as catalase, peroxiredoxin 1, Parkinson disease 7, and stress-induced phosphoprotein 1 can contribute to the secondary injury of spinal cord. Decreases of development-related 3-phosphoglycerate dehydrogenase and stathmin 1 may be not propitious for spinal cord regeneration. On the other hand, increases of isocitrate dehydrogenase 3 alpha/gamma and glutamate dehydrogenase 1 can help compensate the impaired energy metabolism. Increases of sirtuin 2, crystallin alpha B (CRYAB), and heat shock 27-kDa protein 1 can help resist stresses induced by injury. Increases of adenylate cyclase-associated protein 1 and galactose binding lectin 3 can help regeneration by replaying their roles in neural development. To our knowledge, this is the first case of characterization of the proteomic changes seen in the precipitated fraction of injured spinal cord. Most of the identified proteins were found for the first time to be differentially expressed after spinal cord injury, which may provide new clues about the molecular mechanisms of spinal cord injury and repair.
 ...
PMID:Proteomic profiling of the insoluble pellets of the transected rat spinal cord. 1911 13

The present study deals with the transformation of L-tyrosine to L-dopa by Acremonium rutilum, a fungal tyrosinase producer, isolated from decomposed banana stud. This appears to be the first report on A. rutilum as a polyphenoloxidase producer with both cresolase and catecholase activity. Enriched Czapek-Dox agar was used for plate assay screening. Enriched potato dextrose broth was used for optimization studies, which induced high levels of L-dopa under submerged fermentation. A. rutilum gave the maximum L-dopa production (0.89 mg/ml) and tyrosinase activity (1095 U/mg) under the optimized parameters, that is, a temperature of 25 degrees C, pH 5.5, an inoculum size of 2.5 ml, and an incubation time of 72-120 h, with L-tyrosine (5 mg/ml) as substrate. Five resolved bands, with R(f) values of 0.73, 0.60, 0.54, 0.37, and 0.26, were observed, which confirmed the presence of L-dopa. This study involves the elevated profile of L-dopa production. Such study is needed, as L-dopa has the ability to control Parkinson's disease.
 ...
PMID:Transformation of L-tyrosine to L-dopa by a novel fungus, Acremonium rutilum, under submerged fermentation. 1912 33

DJ-1, a causative gene product of a familial form of Parkinson's disease (PD), PARK7, plays a role in anti-oxidative stress, and loss of its function is thought to result in the onset of PD. Superfluous oxidation of cysteine at amino acid 106 (C106) of DJ-1 renders DJ-1 inactive, and such oxidized DJ-1 was observed in patients with the sporadic form of PD. In this study, we examined the relationship between DJ-1 and compounds extracted from traditional Chinese medicines possessing anti-oxidant activity. Of the 12 compounds tested, 5 were found to specifically bind to the C106 region by using a quartz crystal microbalance. Although 4 compounds prevented rat PC12 and primary neuronal cells from undergoing H2O2-induced cell death, the protective activity of 2 compounds, kaempferol 3-O-beta-rutinoside and 6-hydroxykaempferol 3,6-di-O-beta-D-glucoside, was diminished in cells transfected with siRNA targeting DJ-1, indicating DJ-1-dependent reaction of these compounds. Furthermore, these compounds reduced the level of reactive oxygen species and restored tyrosine hydroxylase activity that had been induced and compromised, respectively, by treatment of cells with H2O2. The results suggest that these compounds are useful lead compounds for PD therapy.
 ...
PMID:Kaempferol derivatives prevent oxidative stress-induced cell death in a DJ-1-dependent manner. 1949 71

Immunomodulatory effects of transplanted mesenchymal stem cells (MSCs) in the treatment of Parkinson's disease were studied in the MPTP-induced mouse model. MPTP treatment induced a significant loss of dopaminergic neurons, decreased expressions of claudin 1, claudin 5 and occludin in the substantia nigra compacta (SNc), and functional damage of the blood brain barrier (BBB). Our study further discovered that infiltration of MBLs into the brain to bind with microglia was detected in the SNc of MPTP-treated mice, suggesting that the BBB compromise and MBL infiltration might be involved in the pathogenesis of MPTP-induced PD. In addition, MPTP treatment also increased the expression of mannose-binding lectins (MBLs) in the liver tissue. Intravenous transplantation of MSCs into MPTP-treated mice led to recovery of BBB integrity, suppression of MBL infiltration at SNc and MBL expression in the liver, suppression of microglial activation and prevention of dopaminergic neuron death. No transplanted MSCs were observed to differentiate into dopaminergic neurons, while the MSCs migrated into the SNc and released TGF-beta1 there. Therefore, intravenous transplantation of MSCs which protect dopaminergic neurons from MPTP toxicity may be engaged in anyone or a combination of these mechanisms: repair of the BBB, reduction of MBL in the brain, inhibition of microglial cytotoxicity, and direct protection of dopaminergic neurons.
 ...
PMID:Mesenchymal stem cell transplantation attenuates blood brain barrier damage and neuroinflammation and protects dopaminergic neurons against MPTP toxicity in the substantia nigra in a model of Parkinson's disease. 1981 31


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>