Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1852438 (CCL)
 1,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Studies of the retina in 6- and 22-month-old English setters with progressive blindness, ataxia, and muscle weakness demonstrated a marked accumulation of abnormal cytosomes within neurons and retinal pigmented epithelial cells. Ganglion cells contained abundant cytosomes with evenly spaced stacks of membranes; bipolar and amacrine cell cytosomes consisted of dense, amorphous material with closely spaced configurations of light and dark lines; cytosomes within photoreceptor cells contained faintly staining curved profiles. All three cytosomes resembled those previously reported in brain neurons of CCL dogs. In retinal pigmented epithelial cells, there were prominent accumulations of lamellar fragments, either free in the cytoplasm or incorporated into melanin granules. These retinal abnormalities are likely to be related to deficiences of peroxidase and defects of lipid peroxidation. The pathologic and biochemical changes seen in these dogs are similar in many respects to those reported in human patients with Batten disease. As such, these dogs provide a convenient model for the study disease mechanisms and for therapeutic approaches to blindness in Batten disease.
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PMID:Studies on the retina and the pigment epithelium in hereditary canine ceroid lipofuscinosis. III. Morphologic abnormalities in retinal neurons and retinal pigmented epithelial cells. 735 Jan 37

The underlying cause of the selective death of the nigral dopaminergic neurons in Parkinson's disease is not fully understood. Tetrahydrobiopterin (BH4) is synthesized exclusively in the monoaminergic, including dopaminergic, cells and serves as an endogenous and obligatory cofactor for syntheses of dopamine and nitric oxide. Because BH4 contributes to the syntheses of these two potential oxidative stressors and also undergoes autoxidation, thereby producing reactive oxygen species, it was possible that BH4 may play a role in the selective vulnerability of dopaminergic cells. BH4 given extracellularly was cytotoxic to catecholamine cells CATH. a, SK-N-BE(2)C, and PC12, but not to noncatecholamine cells RBL-2H3, CCL-64, UMR-106-01, or TGW-nu-1. This was not caused by increased dopamine or nitric oxide, because inhibition of their syntheses did not attenuate the damage and BH4 did not raise their cellular levels. Dihydrobiopterin and biopterin were not toxic, indicating that the fully reduced form is responsible. The toxicity was caused by generation of reactive oxygen species, because catalase, superoxide dismutase, and peroxidase protected the cells from the BH4-induced demise. Furthermore, thiol agents, such as reduced glutathione, dithiothreitol, beta-mercaptoethanol, and N-acetylcysteine were highly protective. The BH4 toxicity was initiated extracellularly, because elevation of intracellular BH4 by sepiapterin did not result in cell damage. BH4 was spontaneously released from the cells of its synthesis to a large extent, and the release was not further enhanced by calcium influx. This BH4-induced cytotoxicity may represent a mechanism by which selective degeneration of dopaminergic terminals and neurons occur.
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PMID:Tetrahydrobiopterin is released from and causes preferential death of catecholaminergic cells by oxidative stress. 1095 58

Human ceroid-lipofuscinosis is marked by blindness, dementia, ataxia, and premature death. A canine model for this disease exists in English setters whose clinical, pathological and biochemical changes resemble the human disorder. In both syndromes, autofluorescent lipopigments, i.e.; lipofuscin and ceroid ("granular", "fingerprint" and/or "curvilinear bodies") are found in the nervous system, viscera, retina, and pigment epithelium (RPE). Retinal neurons of affected animals between 6 and 22 months of age, contain a variety of abnormal intracellular pigment inclusions. Pigment epithelial cells also contain distinctive cytosomes. Electroretinograms from affected animals showed a reduction in b-wave amplitude. Leukocyte, retinal, and RPE peroxidases, were decreased in affected animals, and also showed age-related changes. In the normal canine eye, peroxidase was associated with fractions containing plasma membranes and melanolysosomes. Improved fractionation techniques localized normal peroxidase to "heavy" fractions (1.24-1.28 g/ml), and peroxidase was decreased in these fractions in CCL animals. A new particle containing hexosaminidase, galactosidase, and acid lipase was observed in affected animals. When retinal homogenates from CCL dogs were injected into the vitreous of rabbit eyes they completely abolished the ERG recording. No such change was observed with homogenates from unaffected animals. The accumulation of large numbers of dense bodies in the retina and RPE in dogs with CCL, along with a decrease in peroxidase, suggests an impairment of degradative mechanisms. Furthermore, ceroid appears to be cytotoxic to the retina and RPE. The relationship of these cytotoxic properties to the accumulation of ceroid in the eye, is the subject of our future research.
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PMID:Morphological and biochemical abnormalities in a model of retinal degeneration: Canine ceroid-lipofuscinosis (CCL). 2048 51