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)

We report the case of a 64 year old woman treated for 10 years by DOPA for Parkinson's disease and displaying brown urine. Homogentisic acid was found in urine, establishing the diagnosis of alkaptonuria. Clinical and radiological studies demonstrated ochronosis and ochronotic arthropathy, blue pigmentation of ear cartilage and calcification of the intervertebral lumbar disc giving the classical "inverted spine". Interrelation between this metabolic abnormality and Parkinson's disease is discussed. The recent cloning and mapping of the human gene for alkaptonuria to chromosome 3q should bring some clarification among relationships between these two diseases.
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PMID:[Parkinson disease and alkaptonuria: fortuitous association or striatonigral ochronosis?]. 767 34

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

Alkaptonuria (AKU) is an ultra-rare disease developed from the lack of homogentisic acid oxidase activity, causing homogentisic acid (HGA) accumulation that produces a HGA-melanin ochronotic pigment, of unknown composition. There is no therapy for AKU. Our aim was to verify if AKU implied a secondary amyloidosis. Congo Red, Thioflavin-T staining and TEM were performed to assess amyloid presence in AKU specimens (cartilage, synovia, periumbelical fat, salivary gland) and in HGA-treated human chondrocytes and cartilage. SAA and SAP deposition was examined using immunofluorescence and their levels were evaluated in the patients' plasma by ELISA. 2D electrophoresis was undertaken in AKU cells to evaluate the levels of proteins involved in amyloidogenesis. AKU osteoarticular tissues contained SAA-amyloid in 7/7 patients. Ochronotic pigment and amyloid co-localized in AKU osteoarticular tissues. SAA and SAP composition of the deposits assessed secondary type of amyloidosis. High levels of SAA and SAP were found in AKU patients' plasma. Systemic amyloidosis was assessed by Congo Red staining of patients' abdominal fat and salivary gland. AKU is the second pathology after Parkinson's disease where amyloid is associated with a form of melanin. Aberrant expression of proteins involved in amyloidogenesis has been found in AKU cells. Our findings on alkaptonuria as a novel type II AA amyloidosis open new important perspectives for its therapy, since methotrexate treatment proved to significantly reduce in vitro HGA-induced A-amyloid aggregates.
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PMID:Alkaptonuria is a novel human secondary amyloidogenic disease. 2285 Apr 26