Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.6.3.14 (ATP synthase)
 7,042 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this study, we show that two biochemical markers of neuronal ceroid lipofuscinoses (NCLs) are present in a mutant mouse (mnd/mnd) that exhibits symptoms of the disease. Subunit c of the mitochondrial F1F0-ATP synthase, a proteolipid that accumulates in storage bodies of most forms of NCL and several animal models, is dramatically increased in mnd/mnd mouse brain, kidney, liver, heart, and pancreas. Interestingly, another related proteolipid, subunit c of the vacuolar H(+)-ATPase, also accumulates in several mnd/mnd tissues. The molar ratio of the vacuolar subunit c to the F1F0 subunit c is approximately one to two in enriched storage bodies from brain. The relative accumulation of the vacuolar subunit c correlates with its abundance in normal tissues. It appears in decreasing amounts in brain, kidney, and liver and is not detected in heart or pancreas. Aged mice and two mutant mouse lines, juvenile bare (jb) and mucopolysaccharidosis, type VII (gusmps), did not accumulate either of these proteolipids. Dolichol-linked oligosaccharides also accumulate in NCLs and are increased 17-fold in mnd/mnd mouse brain. Thus, mnd/mnd mice seem to be an excellent model for NCLs since they not only share clinical signs and histopathology, but also two biochemical markers. The accumulation of the vacuolar subunit c in this model may prove to be a marker for distinguishing different forms of NCLs.
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PMID:Two related proteolipids and dolichol-linked oligosaccharides accumulate in motor neuron degeneration mice (mnd/mnd), a model for neuronal ceroid lipofuscinosis. 814 16

Immunohistochemical and biochemical studies of subunit c of mitochondrial ATP synthase (SCMAS) storage were carried out in neuronal ceroid lipofuscinosis (NCL) and in a series of unrelated inherited and acquired lysosomal disorders. In the NCL group, represented by the late infantile, early juvenile and juvenile types, SCMAS storage was generalized neurovisceral, with considerable difference in the visceral storage pattern between the types. In late infantile NCL the SCMAS storage was intensive and corresponded to the generalized, autofluorescent, uniformly curvilinear material, irrespective of the cell type affected. In both early juvenile and juvenile NCLs the SCMAS storage was strong and almost uniform in brain neurons, but did not correlate entirely with the visceral autofluorescent storage pool, being undetectable in autofluorescent storage deposits in a constant set of tissues. In the adult (Kufs) type, the brain neurons were stained with various intensity. In infantile NCL, SCMAS storage was restricted to some of the persisting neurons. In a series of inherited lysosomal enzymopathies and acquired lysosomal disorders, excessive SCMAS accumulation was found only in secondary neuronal lipopigments. It occurred as an early and more uniform phenomenon in mucopolysaccharidosis types I, II, IIIA and in polysulphatase deficiency, or as a delayed varied phenomenon in protracted variants of mucolipidosis I, Niemann-Pick types A and C, and GM2 and GM1 gangliosidoses. Neuronal ageing led to an irregular increase in immunodetectable SCMAS epitope in some neuronal lipofuscin granules. There was no evidence of significant SCMAS lysosomal accumulation in non-neural cells in the whole group, regardless of whether lipofuscin or ceroid accumulation occurred or not. The neuronal SCMAS storage is thus nosologically a common unspecific phenomenon, which is especially amplified in NCL. The specificity of the NCL storage process is shown by the fact that even lysosomes of non-neuronal cells in NCL accumulate SCMAS.
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PMID:Follow-up study of subunit c of mitochondrial ATP synthase (SCMAS) in Batten disease and in unrelated lysosomal disorders. 911 3

Mucopolysaccharidosis IIIB (MPS IIIB) is a lysosomal storage disorder caused by mutations in NAGLU, the gene encoding alpha-N-acetylglucosaminidase. The disease is characterized by profound mental retardation and eventual neurodegeneration, but relatively mild somatic manifestations. There is no available therapy. We have used a mouse knockout model of the disease to test therapy by genetically modified bone marrow. Bone marrow from Naglu -/- male mice was transduced with human NAGLU cDNA in an MND-MFG vector, and transplanted into 6- to 8-week-old lethally irradiated female -/- mice. Sham-treated mice received bone marrow transduced with eGFP cDNA in an MND vector. alpha-N-Acetylglucosaminidase activity in plasma and leukocytes, measured 3 and 6 months after transplantation, varied from marginal to nearly 30 times wild-type. A low level of alpha-N-acetylglucosaminidase activity, as little as provided by transplantation of unmodified Naglu +/+ bone marrow, could normalize biochemical defects (glycosaminoglycan storage and beta-hexosaminidase elevation) in liver and spleen, but a very high level was required for an effect on kidney. Effects on the brain were best seen by examination of cellular morphology using light and electron microcopy. Mice that expressed very high levels of alpha-N-acetylglucosaminidase in blood had an increased number of normal-appearing neurons in the cortex and other parts of the brain, while microglia with engorged lysosomes had almost completely disappeared. Immunohistochemistry showed a marked decrease of staining for subunit c of mitochondrial ATP synthase and for Lamp1, markers of neuronal and microglial pathology, respectively, as well as a decrease in staining for glial fibrillary acid protein, a marker of activated astrocytes. These results show that genetically modified cells of hematopoietic origin can reduce the pathologic manifestations of MPS IIIB in the Naglu -/- mouse brain.
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PMID:Retrovirally transduced bone marrow has a therapeutic effect on brain in the mouse model of mucopolysaccharidosis IIIB. 1530 26