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)

The plasma soluble melanins (PSM) form spontaneously in vitro and in vivo and their formation involves oxidative polymerization and copolymerization of dopa, catecholamines, homogentisic acid, 3-hydroxyanthranilic acid, p-aminophenol, p-phenylenediamine, and other end(ex)ogenous ortho and para polyhydroxy-, (poly)hydroxy(poly)amino- and polyamino-phenyl compounds. The build up of PSM is visible within 2-3 h after the start of incubation at 37 degrees C with 1 mg/ml of plasma. PSM also form similarly in blood and these processes cause hemolysis. The mean quantity of PSM in normal human plasma is 1.61+/-0.1 (S.D.) mg/ml (n = 20) and in normal human urine is 1.1+/-1.2 g/24 h collection (n = 8). They contribute to the yellow color of plasma and urine. Antioxidants delay the formation of PSM. The deposited melanins also form from these precursors. Reactive oxygen side products (ROSP) are generated during and after melanogenesis. Melanins in vivo are generally associated with proteins or with proteins and lipids. The PSM-protein-lipid complexes are called plasma soluble lipofuscins (PSL), because they have histochemical and fluorescence properties similar to those of solid lipofuscins. The soluble and deposited melanins (SDM) and their intermediates have similar toxic chemical reactivities. The oxidizing quinoid (they can produce partially and completely substituted conjugates) and the semiquinoid free radical intermediates are also moieties in most human melanin structures. Soluble melanins formed from dopa, or dopamine, or norepinephrine in weak alkaline solution have been shown to be toxic to human CD4+ lymphoblastic cells (MT-2) at higher than 10 microg/ml concentrations. Alkaptonuria with high levels of homogentisic acid in the plasma is a potentially fatal disease, exhibiting the toxic effects of the homogentisic acid melanin (soluble and deposited), its intermediates and the ROSP. Patients with alkaptonuria develop arthritis and often suffer from other diseases too, including cardiovascular disease (frequent cause of death) and kidney disease. Pheochromocytoma, with high levels of catecholamines in the plasma is another potentially fatal disease. The catecholamine PSM of pheochromocytoma have very light yellow or practically no colors, due to the concentrations and chemical structures. Pheochromocytomas can cause hypertension, cardiovascular disease (frequent cause of death), kidney disease, stroke, cancer, amyloid formation and can mimic many other diseases, including acute pancreatitis, carcinoid, neuroblastoma, psychiatric illness, hypercalcemia, retinal vascular lesions, and diabetes mellitus. Pheochromocytoma is potentially fatal even in patients without hypertension. Following trauma and surgery, heavily pigmented eyes are apt to experience greater inflammation than lightly pigmented eyes. In Parkinson's disease those neurons are lost first in the substantia nigra and locus ceruleus which contain the greatest amounts of neuromelanins. The antihypertensive alphamethyldopa causes Parkinson's syndrome. It forms PSM in a short time in vitro. The side effects of L-dopa (immobility episodes alternate with normal or involuntary movements; psychotic abnormalities) suggest that the SDM, their intermediates and the ROSP present naturally in vivo are involved in the cause of Parkinson's disease and Alzheimer's disease. There is a large overlap between these two diseases. (ABSTRACT TRUNCATED)
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PMID:The probable involvement of soluble and deposited melanins, their intermediates and the reactive oxygen side-products in human diseases and aging. 1124 35

In recent years, a considerable amount of research has been focused on the underlying mechanisms of electroacupuncture and moxibustion assisted tissue repair. Intracellular protein denaturation is a significant pathological step of acute conditions such as stroke, myocardial infarction and acute pancreatitis. Protein aggregation can be observed after the protein denaturation step in chronic diseases of the central nervous system like Alzheimer's and Parkinson's disease, and also in other chronic system diseases including cataract formation. Heat shock proteins (HSPs) are fundamental for intracellular protein repair and work by preventing protein aggregation and assisting denaturated proteins to refold. Further, HSPs can also function for extracellular cell signalling. The focus of this review is to analyse the data studying electroacupuncture and moxibustion induced HSPs, and how acupuncture can survive cells from apoptosis under stress.
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PMID:A review of the potential effect of electroacupuncture and moxibustion on cell repair and survival: the role of heat shock proteins. 1994 27

The pancreas consists of two major divisions, the exocrine and the endocrine pancreas. Recent data from our laboratory have shown that the functions of the two divisions are under modulatory regulation by separate neurocircuits that originate in the dorsal motor nucleus of the vagus (DMV). Metabotropic glutamate receptors (mGluRs) are expressed throughout the central nervous system and have been implicated in the modulation of synaptic transmission. mGluRs consist of three groups of receptors, which can be distinguished based on their pharmacological properties and second messenger systems. Group I mGluRs predominantly increase, whereas group II and III mGluRs decrease synaptic transmission. Group II and group III mGluRs are present on excitatory and inhibitory synaptic terminals impinging on pancreas-projecting DMV neurons. We have shown that group II mGluRs regulate both exocrine pancreatic secretions and insulin release, whereas group III mGluRs only regulate insulin release. Several mGluR agonists and antagonists have been shown to have clinical uses for disorders accompanied by abnormal synaptic transmission, including anxiety and Parkinson's disease. Moreover, a negative allosteric modulator of Group I mGluRs is effective in alleviating symptoms of gastro-esophageal reflux disease (GERD). Since the role of the three mGluR groups in mediating different gastrointestinal (GI) functions appears to be highly specific, the use of agonists or antagonists directed at a single receptor group could potentially provide highly selective targets for the treatment of GI disorders including GERD, functional dyspepsia and acute pancreatitis.
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PMID:Role of metabotropic glutamate receptors in the regulation of pancreatic functions. 2435 65

The recent clinical availability of the PARP inhibitor olaparib (Lynparza) opens the door for potential therapeutic repurposing for non-oncological indications. Considering (a) the preclinical efficacy data with PARP inhibitors in non-oncological diseases and (b) the risk-benefit ratio of treating patients with a compound that inhibits an enzyme that has physiological roles in the regulation of DNA repair, we have selected indications, where (a) the severity of the disease is high, (b) the available therapeutic options are limited, and (c) the duration of PARP inhibitor administration could be short, to provide first-line options for therapeutic repurposing. These indications are as follows: acute ischaemic stroke; traumatic brain injury; septic shock; acute pancreatitis; and severe asthma and severe acute lung injury. In addition, chronic, devastating diseases, where alternative therapeutic options cannot halt disease development (e.g. Parkinson's disease, progressive multiple sclerosis or severe fibrotic diseases), should also be considered. We present a preclinical and clinical action plan for the repurposing of PARP inhibitors.
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PMID:Opportunities for the repurposing of PARP inhibitors for the therapy of non-oncological diseases. 2821 92

Parkinson's disease (PD) is a neurodegenerative disorder with motor and non-motor impairment. It has been known for a while that oxidative stress, protein changes and mitochondrial dysfunction have the role of contribution to the pathogenesis. Disturbance of red blood cell function may play a role in the pathophysiology of neurodegenerative diseases such as Huntington's, Parkinson's and Alzheimer's disease. RDW was found to be strongly associated with inflammatory markers in diseases such as acute pancreatitis, myocardial injury and hepatocellular carcinoma. The data about RDW levels and PD are scarce. In this study, we aimed to investigate the RDW values and their relationship with the severity of the disease in patients with Parkinson's disease. 94 patients with Parkinson's disease were included into the study, 97 healthy individuals without history of PD were considered as control group. The United Parkinson's Disease Rating Scale (UPDRS) and the modified Hoehn and Yahr staging scale were used to assess the severity of PD. Although RDW levels were significantly higher than the healthy subjects, there was not any relation between the severity of PD, duration of the disease, RDW levels, other blood parameters, mean UPDRS score or mean mH&Y score. In conclusion, RDW levels are higher than the healthy subjects in PD patients but there is no relation between RDW levels and disease duration. Larger studies are needed to explain the role of RDW as an inflammatory marker.
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PMID:Red cell distribution width levels in Parkinson's disease patients. 3136 45