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)

Artificial insemination donor selection requires predicting which men are likely to beget the healthiest offspring. Methods are developed for calculating the "offspring excess recurrence risk", delta R, for an anomaly in the offspring of an afflicted father. Mainly from published family survey and population data delta R is computed for 38 disorders. From a small survey a value for the with-treatment "affliction burden", Bt, is assigned to each anomaly. For each disorder the "offspring excess burden expectation" is delta RBt. Defects such as cataract, hereditary Parkinson disease, psoriasis, seropositive rheumatoid arthritis, and schizophrenia have such a high delta RBt that they are individually sufficient cause for rejecting a donor candidate. A candidate may be rejected because of a combination of lesser defects with sigma delta RBt exceeding an acceptable limit. A limit should also be placed on Bt, because the affliction burden for Tay-Sachs disease or cystic fibrosis is intolerable, however infrequent. Most of the important hereditary defects are late onset, and for the older donor the opportunity to select more directly against late-onset disorders offsets the added risk of newly-arising gene mutations. The most careful donor selection cannot completely eliminate the risk of a child inheriting some disorder, but selection can reduce the average total burden by as much as 17%.
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PMID:Selection against genetic defects in semen donors. 646 72

A number of the lysosomal storage diseases that have now been characterized are associated with intra-lysosomal accumulation of lipids, caused by defective lysosomal enzymes. We have previously reported neuronal accumulation of both alpha- and beta-synucleins in brain tissue of a GM2 gangliosidosis mouse model. Although alpha-synuclein has been implicated in several neurodegenerative disorders including Parkinson's disease, dementia with Lewy bodies and multiple system atrophy, its functions remain largely unclear. In our present study, we have examined a cohort of human lipidosis cases, including Sandhoff disease, Tay-Sachs disease, metachromatic leukodystrophy, beta-galactosialidosis and adrenoleukodystrophy, for the expression of alpha- and beta-synucleins and the associated lipid storage levels. The accumulation of alpha-synuclein was found in brain tissue in not only cases of lysosomal storage diseases, but also in instances of adrenoleukodystrophy, which is a peroxisomal disease. alpha-synuclein was detected in both neurons and glial cells of patients with these two disorders, although its distribution was found to be disease-dependent. In addition, alpha-synuclein-positive neurons were also found to be NeuN-positive, whereas NeuN-negative neurons did not show any accumulation of this protein. By comparison, the accumulation of beta-synuclein was detectable only in the pons of Sandhoff disease cases. This differential accumulation of alpha- and beta-synucleins in human lipidoses may be related to functional differences between these two proteins. In addition, the accumulation of alpha-synuclein may also be a condition that is common to lysosomal storage diseases and adrenoleukodystrophies that show an enhanced expression of this protein upon the elevation of stored lipids.
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PMID:Neuronal and glial accumulation of alpha- and beta-synucleins in human lipidoses. 1765 58

Saccades are rapid shifts of gaze that normally place the line of sight on a desired target with a single smooth movement. A number of disease states have been shown to result in saccadic movements that are fragmented, but still end near target position after a multi-step sequence of saccades. Among these disorders are Parkinson's disease and late-onset Tay-Sachs disease (LOTS). We have recently shown that normal human subjects and monkeys also make some two-step saccadic responses in cognitively difficult, choice response tasks. In monkeys we have been able to record neuronal responses as the animals performed a visually guided, choice saccade task. We compared the activity of neurons in the superior colliculus (SC) and the cortical frontal eye field (FEF) during the majority of trials that were accomplished with single-step saccades with those completed with two-step saccades. Several differences in discharge pattern aligned on the first saccade were uncovered. Neurons in the rostral and caudal SC were not modulated at the time of the first saccade, but a class of FEF neurons showed a burst of activity before the first saccade. If these neurons are among those known to project to the saccade generator in the brainstem, they could trigger the onset of a saccade before the remaining machinery in the saccade generator had sufficient activity to sustain the saccade. Overall the results suggest that a delicate balance of triggering and sustaining inputs are required to produce normal single-step saccades. These neural results may also help to clarify the pathology present when fragmented saccades occur in various disease states.
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PMID:Frontal eye field signals that may trigger the brainstem saccade generator. 1871 88

Glycosphingolipids (GSLs) are a specialized class of membrane lipids composed of a ceramide backbone and a carbohydrate-rich head group. GSLs populate lipid rafts of the cell membrane of eukaryotic cells, and serve important cellular functions including control of cell-cell signaling, signal transduction and cell recognition. Of the hundreds of unique GSL structures, anionic gangliosides are the most heavily implicated in the pathogenesis of lysosomal storage diseases (LSDs) such as Tay-Sachs and Sandhoff disease. Each LSD is characterized by the accumulation of GSLs in the lysosomes of neurons, which negatively interact with other intracellular molecules to culminate in cell death. In this review, we summarize the biosynthesis and degradation pathways of GSLs, discuss how aberrant GSL metabolism contributes to key features of LSD pathophysiology, draw parallels between LSDs and neurodegenerative proteinopathies such as Alzheimer's and Parkinson's disease and lastly, discuss possible therapies for patients.
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PMID:Metabolism of Glycosphingolipids and Their Role in the Pathophysiology of Lysosomal Storage Disorders. 3296 78