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 Parkinson-syndrome is the most important syndrome under the extrapyramidal disease. The therapy with L-DOPA has a prominent place in the therapy of Parkinson disease since the introduction of oral effective drugs. Dopamin has an effect to the basalganglia as a neurotransmitter and perhaps an inhibition effect to specific synapses of brain. The inhibition or the optimal balance of the cholinergic systems is the effect of Dopamin and Noradrenalin. The therapy with low dosis of L-DOPA in combination with a decarboxylase-inhibitor will be prevent the side-effects of nerv-cells.
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PMID:[Thoughts on the neurobiological aspects of Parkinson syndrome]. 301 Mar 57

25% of patients with Parkinson's disease demonstrate the first symptoms with 70 years. The deficiency of Tyrosinhydroxylase is the trigger of the decreased level of Dopamin in the basal ganglia. The implications are the typical symptoms (tremor, rigor and akinesia) and the psychopathological decompensations as depression, delirs and bradyphrenie.
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PMID:[Senile Parkinsonism: its motor and psychological defects]. 612 32

The mechanism of the wearing-off phenomenon and the method of how to control it by means of anti-parkinsonian medications is described. To control the wearing-off phenomenon, it is useful to administer L-dopa before eating because absorption of L-dopa is less when competing with amino acids. Administration of L-dopa four or five times a day is also useful. Dopamin agonists(e.g., bromocriptine, pergolide, talipexole, and cabergoline), and monoamine oxidase inhibitors(e.g., selegiline) control the wearing-off phenomenon, and may also suppress its occurrence. As a specific method for controlling the wearing-off phenomenon, continuous administration of anti-parkinsonian drugs by the intra-alimentary tract or a subcutaneous injection is useful. It is important to avoid early wearing-off phenomenon when treating patients with Parkinson's disease.
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PMID:[Wearing-off phenomenon--neurological approach]. 1106 54

The autoxidation and monoamine oxidase (MAO)-mediated metabolism of dopamine (3-hydroxytyramine; DA) cause a continuous production of hydroxyl radical (*OH), which is further enhanced by the presence of iron (ferrous iron, Fe(2+) and ferric ion, Fe(3+)). The accumulation of hydrogen peroxide (H2O2) in the presence of Fe(2+) appears to discard the involvement of the Fenton reaction in this process. It has been found that the presence of DA significantly reduces the formation of thiobarbituric acid reagent substances (TBARS), which under physiological conditions takes place in mitochondrial preparations. The presence of DA is also able to reduce TBARS formation in mitochondrial preparations even in the presence of iron (Fe(2+) and Fe(3+)). However, DA boosted the carbonyl content of mitochondrial proteins, which was further increased in the presence of iron (Fe(2+) and Fe(3+)). This latter effect is also accompanied by a significant reduction in thiol content of mitochondrial proteins. It has also been observed how the pre-incubation of mitochondria with pargyline, an acetylenic MAO inhibitor, reduces the production of *OH and increases the formation of TBARS. Although, the MAO-mediated metabolism of DA increases MAO-B activity, the presence of iron inhibits both MAO-A and MAO-B activities. Consequently, DA has been shown to be a double-edged sword, because it displays antioxidant properties in relation to both the Fenton reaction and lipid peroxidation and exhibits pro-oxidant properties by causing both generation *OH and oxidation of mitochondrial proteins. Evidently, these pro-oxidant properties of DA help explain the long-term side effects derived from l-DOPA treatment of Parkinson's disease and its exacerbation by the concomitant use of DA metabolism inhibitors.
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PMID:Autoxidation and MAO-mediated metabolism of dopamine as a potential cause of oxidative stress: role of ferrous and ferric ions. 1508 28

The structural and functional organization of the cerebral dopaminergic system is considered. The synthesis of dopamine, distribution of dopaminergic structures, structure and classification of dopamin receptors in the brain, and functions of dopamine are discussed. Dopamin among the main catecholamine neurotransmitters participating in the control of locomotor activity, cognition, emotion, positive reinforcement, food intake, and endocrine regulation. Moreover, several neurological diseases such as Parkinson's disease, schizophrenia, and hyperprolactinemia are associated with dysregulation of dopaminergic neurotransmission. Therefore, the search for and development of new dopaminergic drugs is of great interest.
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PMID:[Structural and functional organization of the cerebral dopaminergic system]. 1964 93

Dopamine (3-hydroxytyramine) is a well-known catecholamine neurotransmitter involved in multiple physiological functions including movement control. Here we report that the major extracellular metabolite of dopamine, 3-methoxytyramine (3-MT), can induce behavioral effects in a dopamine-independent manner and these effects are partially mediated by the trace amine associated receptor 1 (TAAR1). Unbiased in vivo screening of putative trace amine receptor ligands for potential effects on the movement control revealed that 3-MT infused in the brain is able to induce a complex set of abnormal involuntary movements in mice acutely depleted of dopamine. In normal mice, the central administration of 3-MT caused a temporary mild hyperactivity with a concomitant set of abnormal movements. Furthermore, 3-MT induced significant ERK and CREB phosphorylation in the mouse striatum, signaling events generally related to PKA-mediated cAMP accumulation. In mice lacking TAAR1, both behavioral and signaling effects of 3-MT were partially attenuated, consistent with the ability of 3-MT to activate TAAR1 receptors and cause cAMP accumulation as well as ERK and CREB phosphorylation in cellular assays. Thus, 3-MT is not just an inactive metabolite of DA, but a novel neuromodulator that in certain situations may be involved in movement control. Further characterization of the physiological functions mediated by 3-MT may advance understanding of the pathophysiology and pharmacology of brain disorders involving abnormal dopaminergic transmission, such as Parkinson's disease, dyskinesia and schizophrenia.
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PMID:The dopamine metabolite 3-methoxytyramine is a neuromodulator. 2097 42

The 3-hydroxytyramine/dopamine is a monoamine of the catecholamine group and it is a precursor of the noradrenaline and adrenaline synthesis, in which the enzyme tyrosine hydroxylase acts as a rate-limiting enzyme. The dopaminergic nuclei retrorubral field (A8 group), substantia nigra pars compacta (A9 group) and ventral tegmental area (A10 group) are involved in three complex circuitries named mesostriatal, mesocortical and mesolimbic, which are directly related to various behavioral manifestations such as motor control, reward signaling in behavioral learning, motivation and pathological manifestations of Parkinson's disease and schizophrenia. The aim of this study was to describe the delimitation of A8, A9 and A10 groups and the morphology of their neurons in the brain of the rock cavy (Kerodon rupestris), a typical Brazilian Northeast rodent belonging to the suborder Hystricomorpha, family Caviidae. Coronal and sagittal sections of the rock cavy brains were submitted to Nissl staining and TH immunohistochemistry. The organization of these dopaminergic nuclei in the rock cavy brain is very similar to that found in other animals of the Rodentia order, except for the presence of the tail of the substantia nigra, which is found only in the species under study. The results revealed that, apart some morphological variations, A8, A9 and A10 groups are phylogenetically stable brain structures.
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PMID:A cytoarchitectonic and TH-immunohistochemistry characterization of the dopamine cell groups in the substantia nigra, ventral tegmental area and retrorubral field in the rock cavy (Kerodon rupestris). 2444 14

It is widely known that the catecholamine group is formed by dopamine, noradrenaline and adrenaline. Its synthesis is regulated by the enzyme called tyrosine hydroxylase. 3-hydroxytyramine/dopamine (DA) is a precursor of noradrenaline and adrenaline synthesis and acts as a neurotransmitter in the central nervous system. The three main nuclei, being the retrorubral field (A8 group), the substantia nigra pars compacta (A9 group) and the ventral tegmental area (A10 group), are arranged in the die-mesencephalic portion and are involved in three complex circuitries - the mesostriatal, mesolimbic and mesocortical pathways. These pathways are involved in behavioral manifestations, motricity, learning, reward and also in pathological conditions such as Parkinson's disease and schizophrenia. The aim of this study was to perform a morphological analysis of the A8, A9 and A10 groups in the common marmoset (Callithrix jacchus - a neotropical primate), whose morphological and functional characteristics support its suitability for use in biomedical research. Coronal sections of the marmoset brain were submitted to Nissl staining and TH-immunohistochemistry. The morphology of the neurons made it possible to subdivide the A10 group into seven distinct regions: interfascicular nucleus, raphe rostral linear nucleus and raphe caudal linear nucleus in the middle line; paranigral and parainterfascicular nucleus in the middle zone; the rostral portion of the ventral tegmental area nucleus and parabrachial pigmented nucleus located in the dorsolateral portion of the mesencephalic tegmentum. The A9 group was divided into four regions: substantia nigra compacta dorsal and ventral tiers; substantia nigra compacta lateral and medial clusters. No subdivisions were made for the A8 group. These results reveal that A8, A9 and A10 are phylogenetically stable across species. As such, further studies concerning such divisions are necessary in order to evaluate the occurrence of subdivisions that express DA in other primate species, with the aim of characterizing its functional relevance.
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PMID:Nuclear organization of the substantia nigra, ventral tegmental area and retrorubral field of the common marmoset (Callithrix jacchus): A cytoarchitectonic and TH-immunohistochemistry study. 2729 10