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)

The activities of the aminotransferases, GOT and GPT, were determined in the serum and cerebrospinal fluid of patients with Parkinson's disease, Huntington's chorea, Wilson's disease, amyotrophic lateral sclerosis (ALS), Friedreich's ataxia, phenylketonuria, and head injuries. 1. In patients with Huntington's chorea the activity of SGOT was lower than in controls (P = 0.02); in Friedreich's ataxia LGPT activity was decreased (P less than 0.001); in patients suffering from ALS SGOT (P = 0.005), SGPT (P less than 0.001) and LGOT (P less than 0.001) activities were increased. 2. Long-term treatment of Parkinson's disease and Wilson's disease with L-dopa resulted in an increase in SGOT, LGOT, and SGPT activity over approximately 2 months, with subsequent normalization of these enzyme activities in spite of continued therapy. Guanidine treatment led to an increase in aminotransferase activities in patients with ALS. Penicillamine caused a decrease in SGOT and SGPT activities in Wilson's disease. These results illustrate the necessity of taking therapeutic measures into account in the interpretation of data on aminotransferase activities.
 ...
PMID:[The activity of aminotransferases in serum and cerebrospinal fluid in neurological diseases (author's transl)]. 12 63

Levels of biopterin derivatives in urine, serum, milk, cerebrospinal fluid, brain, and liver have been measured with the Crithidia fasciculata assay. Normal levels in serum and urine have been given and compared with those in a number of benign and malignant proliferative disorders, phenylketonuria, kidney disease, Parkinson's disease, schizophrenia, controlled epilepsy, rheumatoid arthritis, and pernicious anaemia. The active component of Crithidia factor in serum was 7,8-dihydrobiopterin. Tissue, urine, and some serum samples contained two active materials, the principal one being 7,8-dihydrobiopterin; a minor constituent was probably tetrahydrobiopterin. Serum biopterin levels following methotrexate administration were raised and subsequent administration of folic acid and 5-formyltetrahydrofolic acid further increased serum levels of biopterin derivatives; this was in contrast to the total absence of response to oral folates without prior methotrexate and to 5-methyltetrahydrofolic acid either with or without methotrexate being given.
 ...
PMID:Biopterin derivatives in human body fluids and tissues. 93 31

1,2,3,4-Tetrahydroisoquinoline (TIQ) has been reported to occur in human brain, with its content being 10-fold higher in the brain of a patient with Parkinson's disease (PD) than in that of a control subject. This congener of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) could be formed in brain by the condensation of phenylethylamine with metabolically formed formaldehyde. Phenylethylamine contents are greatly increased in the tissues of untreated patients with phenylketonuria. We injected C57 black mice repeatedly with maximal tolerated doses of TIQ, but later found no reduction in the contents of dopamine and its metabolites in their striata. We doubt that TIQ is a cause of PD, especially since the disorder has not been reported to occur in elderly patients with phenylketonuria.
 ...
PMID:Tetrahydroisoquinoline lacks dopaminergic nigrostriatal neurotoxicity in mice. 336 4

Non-enzymatic products of neuroamines and endogenous carbonyl compounds are apparent "normal" products in human metabolism, and their levels become increased during pathological conditions. DA condensation products--salsolinol, its O-methylated derivative, and methylated derivatives of 1-carboxyl-THP--are found normally in human urine, and the last TIQ is in human brain. Potential beta-carboline condensation products also occur in (aging) human lens tissue. Chronic drinking in alcoholics causes significant increases in urinary salsolinol and O-methyl-salsolinol, presumably due to the increased AcH which is made available. L-DOPA therapy (in Parkinson's disease) elevates urinary and tissue levels of the carboxylated THP derivatives, as well as of salsolinol and THP itself; hyperphenylalaninemia during PKU also increases tissue levels of a DA/phenylpyruvate-derived TIQ and an imine condensate of phenylethylamine and vitamin B6. These unusual products may interfere with neural dynamic processes, and produce cytotoxic metabolites.
 ...
PMID:Neuroamine condensations in human subjects. 740 16

Tetrahydrobiopterin (H4-biopterin) is an essential cofactor of a set of enzymes that are of central metabolic importance, i.e. the hydroxylases of the three aromatic amino acids phenylalanine, tyrosine, and tryptophan, of ether lipid oxidase, and of the three nitric oxide synthase (NOS) isoenzymes. As a consequence, H4-biopterin plays a key role in a vast number of biological processes and pathological states associated with neurotransmitter formation, vasorelaxation, and immune response. In mammals, its biosynthesis is controlled by hormones, cytokines and certain immune stimuli. This review aims to summarize recent developments concerning regulation of H4-biopterin biosynthetic and regulatory enzymes and pharmacological effects of H4-biopterin in various conditions, e.g. endothelial dysfunction or apoptosis of neuronal cells. Also, approaches towards gene therapy of diseases like the different forms of phenylketonuria or of Parkinson's disease are reviewed. Additional emphasis is given to H4-biopterin biosynthesis and function in non-mammalian species such as fruit fly, zebra fish, fungi, slime molds, the bacterium Nocardia as well as to the parasitic protozoan genus of Leishmania that is not capable of pteridine biosynthesis but has evolved a sophisticated salvage network for scavenging various pteridine compounds, notably folate and biopterin.
 ...
PMID:Tetrahydrobiopterin biosynthesis, utilization and pharmacological effects. 1200 48

Whereas a growing interest in the development of attentional flexibility (AF) and in perseverative behavior, being one marker of this component, exists in neuropsychological studies and in the domain of developmental psychopathology (e.g., PKU, infantile schizophrenia, autism and Parkinson's disease) (Pennington & Ozonoff, 1996; Stahl & Pry, 2002), only a few studies have concerned themselves with this subject in normal children. It is thus of interest to add more empirical data to the existing literature in this domain. Therefore, the aim of our study was to explore the development of AF and of perseverative errors in young preschool children with normal development, aged 1.5 to 6 years. Using set-shifting tasks of increasing difficulty level, three age groups were compared with respect to their AF skills. Results show a developmental factor underlying AF, with different levels of this form becoming more and more complex with age, ranging from a rudimentary visual form to a complex representational form of flexibility. Overall, few perseverative errors occurred and they decreased with age. Results are discussed from a developmental and neuropsychological perspective.
 ...
PMID:Attentional flexibility and perseveration: developmental aspects in young children. 1603 43

Protein misfolding is a common event in living cells. In young and healthy cells, the misfolded protein load is disposed of by protein quality control (PQC) systems. In aging cells and in cells from certain individuals with genetic diseases, the load may overwhelm the PQC capacity, resulting in accumulation of misfolded proteins. Dependent on the properties of the protein and the efficiency of the PQC systems, the accumulated protein may be degraded or assembled into toxic oligomers and aggregates. To illustrate this concept, we discuss a number of very different protein misfolding diseases including phenylketonuria, Parkinson's disease, alpha-1-antitrypsin deficiency, familial neurohypophyseal diabetes insipidus, and short-chain acyl-CoA dehydrogenase deficiency. Despite the differences, an emerging paradigm suggests that the cellular effects of protein misfolding provide a common framework that may contribute to the elucidation of the cell pathology and guide intervention and treatment strategies of many genetic and age-dependent diseases.
 ...
PMID:Protein misfolding and human disease. 1672 4

Hydroxylation of the aromatic amino acids phenylalanine, tyrosine and tryptophan is carried out by a family of non-heme iron and tetrahydrobiopterin (BH4) dependent enzymes, i.e. the aromatic amino acid hydroxylases (AAHs). The reactions catalyzed by these enzymes are important for biomedicine and their mutant forms in humans are associated with phenylketonuria (phenylalanine hydroxylase), Parkinson's disease and DOPA-responsive dystonia (tyrosine hydroxylase), and possibly neuropsychiatric and gastrointestinal disorders (tryptophan hydroxylase 1 and 2). We attempt to rationalize current knowledge about substrate and inhibitor specificity based on the three-dimensional structures of the enzymes and their complexes with substrates, cofactors and inhibitors. In addition, further insights on the selectivity and affinity determinants for ligand binding in the AAHs were obtained from molecular interaction field (MIF) analysis. We applied this computational structural approach to a rational analysis of structural differences at the active sites of the enzymes, a strategy that can help in the design of novel selective ligands for each AAH.
 ...
PMID:Selectivity and affinity determinants for ligand binding to the aromatic amino acid hydroxylases. 1730 46

Dopamine regulation may play a role in attention-deficit hyperactivity disorder (ADHD). Visual contrast sensitivity has been proposed as a measure of retinal dopamine that may predict frontal lobe dopamine levels. Individuals with disorders involving dopamine dysregulation (e.g., Parkinson's disease, Phenylketonuria) have shown poor contrast sensitivity. In this study, 110 6- to 13-year-old children with and without ADHD completed a task measuring visual contrast sensitivity. As predicted, contrast sensitivity was significantly worse in children with ADHD-Combined Type than controls. Contrast sensitivity was significantly correlated with inattention and hyperactivity. However, unlike many neuropsychological studies of ADHD, only hyperactivity accounted for unique variance.
 ...
PMID:Contrast sensitivity in children with and without attention deficit hyperactivity disorder symptoms. 2018 26

Though a great deal is known of the pathophysiology of phenylketonuria (PKU), Parkinson's disease (PD) and Alzheimer's disease (AD) very little is known regarding possible chemical species responsible for initiating the cascade of events that ultimately cause cognitive dysfunction. Can these be viewed as inborn errors in metabolism, occurring at various stages in the life cycle, analogous to adult onset diabetes? One major deficiency in understanding such conditions is the paucity of information regarding the total metabolic pathway for various amino acids that may be implicated in their causation. For example in PKU, its etiology was reported in 1934 and dietary restriction of phenylalanine proved effective for individuals with unsatisfactory metabolism of phenylalanine. Yet, current phenylalanine metabolism does not take into account fully the multiple biochemical pathways operating whose role is preventing burdensome accumulations of intermediates that can contribute to morbidity and toxicity. The same may apply for metabolism of tyrosine in PD and methionine in AD. Especially important, are the presence of labile and reactive chemical species which may be causative agents in protein alteration, misfolding and the creation of prions in neurodegenerative diseases, thereby preventing normal protein catabolism and excretion. Though genetic or epigenetic factors must be responsible, the question remains how are these translated into the chemical structures responsible for disease initiation? The purpose of this presentation is to explore potential labile metabolites in those biochemical pathways, which may be contributing factors. Finally it is worth noting, that drug development has been increasingly designed based upon targeting genetic deficiencies. The effectiveness of this approach for the treatment of these neurodegenerative illnesses will be determined in the future.
...
PMID:Possible chemical initiators of cognitive dysfunction in phenylketonuria, Parkinson's disease and Alzheimer's disease. 2394 32


1 2 Next >>