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)

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.
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PMID:Proteomic profiling of the insoluble pellets of the transected rat spinal cord. 1911 13

The thalamus plays pivotal roles in the central nervous system as relay center for organizing information, such as auditory and visual senses from diverse brain regions and their re-distribution to the cerebral cortex. Brain diseases including schizophrenia, Parkinson's disease, epilepsy, and bipolar disorder have been associated with the thalamus. We performed a shotgun proteome analysis of iTRAQ-labeled tryptic peptides of human mediodorsal thalamus protein extracts coming from two healthy male and two healthy female subjects. The shotgun workflow consisted of IEF fractionation, RP LC and MALDI-TOF/TOF mass spectrometric analysis. We were able to identify 542 proteins that are involved in different biological processes and from diverse cellular localizations. A considerable fraction of these proteins had not been identified by traditional proteomics methods such as 2-DE. The thalamus proteome contributes to the knowledge of the human brain proteome and future applications in basic and clinical research.
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PMID:Shotgun mass spectrometry analysis of the human thalamus proteome. 1930 23

Research on Parkinson's disease fails to pinpoint a single gene or a gene product as the causative factor. However, the early onset form of the disease may be caused by mutations in PARK2 gene. Some studies related to the biochemistry or other aspects of the PARK2 gene or its product mostly used cDNA generated from substantia nigra of the mid-brain. This is essentially because the presence of the 1.4kb full-length PARK2 cDNA in human leukocytes is, so far, not demonstrated although some splice variants and short RT-PCR products were reported. In this study, we synthesized a 1.4kb full-length PARK2 cDNA from human leukocytes, cloned and expressed it both in Escherichia coli and in HeLa cells. The presence of Parkin protein was also demonstrated in human serum using Western blotting and MALDI-TOF analysis. The results of this study showed a simple way for routine amplification of PARK2 cDNA from human blood and may become a useful diagnostic tool in the future.
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PMID:Evidence for the presence of full-length PARK2 mRNA and Parkin protein in human blood. 1950 Nov 31

Dopamine-HCl and L-DOPA-alpha-glycosides were prepared by reaction with cyclomaltohexaose, catalyzed by Bacillus macerans cyclomaltodextrin glucanyltransferase. The reaction gave maltodextrins attached to dopamine and L-DOPA; the maltodextrins were trimmed by reactions with glucoamylase and beta-amylase to produce alpha-glucosyl- and alpha-maltosyl-glycosides, respectively. The glucoamylase- or beta-amylase-treated dopamine- and L-DOPA-alpha-glycosides were fractionated and purified by BioGel P-2 gel-filtration column chromatography and preparative descending paper chromatography. Analysis by MALDI-TOF mass spectrometry and one- and two-dimensional NMR showed that the purified glycosides of dopamine and L-DOPA were glycosylated at the hydroxyl groups of positions 3 and 4 of the catechol ring. The major product was found to be 4-O-alpha-glycopyranosyl L-DOPA, and it was shown to be more resistant to oxidative tolerance experiments, involving hydrogen peroxide and ferrous ion, than L-DOPA. L-DOPA-alpha-glycosides are possibly more effective substitutes for L-DOPA in treating Parkinson's disease in that they are more resistant to oxidation and methylation, which renders L-DOPA ineffective and deleterious.
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PMID:Synthesis of dopamine and L-DOPA-alpha-glycosides by reaction with cyclomaltohexaose catalyzed by cyclomaltodextrin glucanyltransferase. 1979 83

DJ-1 is an oncogene and also a causative gene for a familial form of Parkinson's disease. DJ-1 has multiple functions, including anti-oxidative stress reaction and cysteine 106 (C106) of DJ-1 is an essential amino acid for DJ-1 to exert its function. While increased expression and secretion of DJ-1 into serum in patients with various cancers and regulation of p53 and PTEN by DJ-1 have been reported, the molecular mechanism underlying oncogenicity of DJ-1 is poorly understood. Here, we analyzed the function of DJ-1 in the PI3'K signaling pathway under an oxidative stress condition, focusing on the interaction of DJ-1 with PTEN. We found that both wild-type (wt) and C106S-DJ-1, a substitution mutant of DJ-1, directly bound to PTEN and inhibited PTEN phosphatase activity but that C106S-DJ-1 more strongly inhibited the activity than did wt-DJ-1. When NIH3T3 cells were treated with H2O2, oxidation of C106 of wt-DJ-1 occurred, accompanied by increased binding of wt-DJ-1 to PTEN, decreased PTEN activity and increased phosphorylation of AKT. C106S-DJ-1 transformed cells more strongly than did wt-DJ-1 and the transforming activity of DJ-1 was enhanced by H2O2 treatment of cells in which increased binding of DJ-1 to PTEN and decreased PTEN activity were observed. Furthermore, TOF-MS analysis of the oxidative status of C106 suggested that DJ-1 activity requires the presence of the reduced form of C106, which accounts for >50% of the total form. These results suggest that the oxidative status of DJ-1 regulates PTEN activity, leading to cell proliferation and transformation.
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PMID:Oxidation of DJ-1-dependent cell transformation through direct binding of DJ-1 to PTEN. 1988 56

Recently, a variant in LINGO1 (also denominated as LRRN6A) rs9652490:A>G gene has been found to associate with increased risk of essential tremor (ET). Because ET and Parkinson's disease (PD) may be ethiologically related, we proceeded to conduct an analysis of the SNP in PD population. In the current study LINGO1 rs9652490:A>G polymorphism was evaluated in a cohort of 162 Polish patients diagnosed with PD and 177 controls by means of MALDI-TOF mass spectrometry. Any significant differences in rs9652490 genotype or allele frequencies between the studied groups were noted. Our findings demonstrate that LINGO1 SNP (rs9652490) is not associated with sporadic PD in our Polish cohort. A meta-analysis of the available data suggests protective role of rs9652490GG genotype (OR 0.70, 95% CI: 0.51-0.96, p=0.028).
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PMID:Analysis of LINGO1 (rs9652490) polymorphism in sporadic Parkinson's disease in a Polish population, and a meta-analysis. 2011 78

In a previous study, a primary culture of midbrain cells was exposed to 9-methyl-beta-carboline for 48 h, which caused an increase in the number of tyrosine hydroxylase-positive cells. Quantitative RT-PCR revealed increased transcription of genes participating in the maturation of dopaminergic neurons. These in vitro findings prompted us to investigate the restorative actions of 9-methyl-beta-carboline in vivo. The compound was delivered for 14 days into the left cerebral ventricle of rats pretreated with the neurotoxin 1-methyl-4-phenyl-pyridinium ion (MPP+) for 28 days applying a dose which lowered dopamine by approximately 50%. Interestingly, 9-methyl-beta-carboline reversed the dopamine-lowering effect of the neurotoxin in the left striatum. Stereological counts of tyrosine hydroxylase-immunoreactive cells in the substantia nigra revealed that the neurotoxin caused a decrease in the number of those cells. However, when treated subsequently with 9-methyl-beta-carboline, the number reached normal values. In search of an explanation for the restorative activity, we analyzed the complexes that compose the respiratory chain in striatal mitochondria by 2-dimension gel electrophoresis followed by MALDI-TOF peptide mass fingerprinting.We found no changes in the overall composition of the complexes. However, the activity of complex I was increased by approximately 80% in mitochondria from rats treated with MPP+ and 9-methyl-beta-carboline compared to MPP+ and saline and to sham-operated rats, as determined by measurements of nicotinamide adenine dinucleotide dehydrogenase activity. Microarray technology and single RT-PCR revealed the induction of neurotrophins: brain-derived neurotrophic factor, conserved dopamine neurotrophic factor, cerebellin 1 precursor protein, and ciliary neurotrophic factor. Selected western blots yielded consistent results. The findings demonstrate restorative effects of 9-methyl-beta-carboline in an animal model of Parkinson's disease that improve the effectiveness of the respiratory chain and promote the transcription and expression of neurotrophin-related genes.
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PMID:9-Methyl-beta-carboline has restorative effects in an animal model of Parkinson's disease. 2036 Jun 14

We have searched for potential biomarkers in the cerebrospinal fluid (CSF) and plasma in an animal model of Parkinson's disease induced by inflammatory challenge. To achieve this, either unilateral or bilateral intranigral injection of lipopolysaccharide (LPS) was performed. CSF proteins were first analyzed either by 2D electrophoresis and MALDI-TOF at days 1 and 10 after the lesion to discern between potential prognosis and diagnosis protein markers. Most significant changes from this analysis were early increases of haptoglobin, transthyretin and different spots further identified as prostaglandin D synthase in response to LPS. These markers were then analyzed by western blotting in CSF and plasma using specific antibodies from samples obtained in animals receiving either LPS in substantia nigra or hippocampus and 6-OHDA in the medial forebrain bundle. This analysis confirmed the early increases of haptoglobin and transthyretin in response to intranigral injection of LPS or 6-OHDA in the bundle in plasma and CSF. We discuss the potential use of both biomarkers for the early diagnose of Parkinson's disease.
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PMID:Use of haptoglobin and transthyretin as potential biomarkers for the preclinical diagnosis of Parkinson's disease. 2055 85

Accumulating evidence suggests that oxidative stress plays a pivotal role in dopaminergic neurodegeneration. However, the kinds of proteins involved in the response to oxidative stress remain unclear. In the present study, SH-SY5Y cells were treated with neurotoxin 1-methyl-4-phenyl-pyridinium ion (MPP+) to induce apoptotic neuronal injury. 2D-DIGE followed by MALDI-TOF-MS was used to determine the changing protein levels. Proteomics analysis revealed that 22 proteins were differentially altered in MPP(+)-treated SH-SY5Y cells, of which 7 were up-regulated proteins and 15 were down-regulated proteins, respectively. Three protein spots were unambiguously identified as sorcin, annexin V, and ribosomal protein P0. The three proteins showed a significant increase in level, suggesting a role in MPP(+)-induced apoptosis. The functional roles of these three proteins collectively indicate that multiple mechanisms are pertinent in the underlying pathogenesis of Parkinson's disease (PD), such as apoptosis, calcium homeostasis, and DNA insults.
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PMID:Proteomics analysis of MPP+-induced apoptosis in SH-SY5Y cells. 2056 39

Parkinson's disease (PD) and atypical parkinsonian disorders (APD), including multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD), are a group of neurodegenerative diseases sharing many similar signs and symptoms but distinguished by their particular clinical features, treatment response, prognosis and mortality. The differential diagnosis may be challenging, especially in early disease stages. Considering the importance of an accurate diagnosis both for clinical management and for research, new diagnostic tools are needed. In this study, we investigated 56 PD, 42 MSA, 39 PSP, 9 CBD patients, and 24 healthy controls. After screening the cerebrospinal fluid (CSF) proteome using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS), we identified 4 proteins (ubiquitin [mass-to-charge ratio (m/z) 8590], beta2-microglobulin [m/z 11730], and 2 secretogranin 1 [chromogranin B] fragments [m/z 7260 and m/z 6250]) that differentiated healthy controls and PD patients from patients with APD. However, they could not differentiate PD patients from controls. As none of these changes were APD subgroup-specific, they most likely reflect the intensity and/or extent of the neurodegenerative process in general.
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PMID:Proteomic profiling of cerebrospinal fluid in parkinsonian disorders. 2062 95


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