Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002736 (amyotrophic lateral sclerosis)
 19,048 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The nicotinic acetylcholine receptor (nAChR) antagonist alpha-bungarotoxin (alpha-Btx) binds to two different classes of high affinity binding sites from the Drosophila central nervous system. We have used the bivalent reagent 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide (EDAC) to cross-link 125I-alpha-Btx (M(r) = 8 kDa) to Drosophila head membranes. Upon sodium dodecylsulphate polyacrylamide gel electrophoresis (SDS-PAGE), one major adduct of M(r) approximately 50 kDa was identified, suggesting that a 42 kDa polypeptide binds the toxin. Adduct formation was inhibited by other cholinergic ligands. Detergent-solubilized receptor complexes containing the cross-linked products were immunoprecipitated by antisera against two nAChR subunits previously identified by molecular cloning, the ALS and ARD proteins, suggesting that the 42 kDa toxin binding polypeptide constitutes a component of the previously described class 1 alpha-Btx binding site.
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PMID:Cross-linking of 125I-alpha-bungarotoxin to Drosophila head membranes identifies a 42 kDa toxin binding polypeptide. 146 70

ALS and ARD proteins are thought to represent a ligand binding and a structural subunit, respectively, of Drosophila nicotinic acetylcholine receptors (nAChRs). Here, antibodies raised against fusion constructs encompassing specific regions of the ALS and ARD proteins were used to investigate a potential association of these two polypeptides. Both ALS and ARD antisera removed 20-30% of the high-affinity binding sites for the nicotinic antagonist 125I-alpha-bungarotoxin (125I-alpha-Btx) from detergent extracts of fly head membranes. Combinations of both types of antisera also precipitated the same fraction of alpha-Btx binding sites, a result suggesting that both polypeptides are components of the previously defined class I 125I-alpha-Btx binding sites in the Drosophila CNS. 125I-alpha-Btx binding to a MS2 polymerase-ALS fusion protein containing the predicted antagonist binding region showed that the ALS protein indeed constitutes the ligand binding subunit of a nicotinic receptor complex. These data are consistent with neuronal nAChRs in Drosophila containing at least two types of subunits, ligand binding and structural ones.
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PMID:Neuronal nicotinic acetylcholine receptors in Drosophila: antibodies against an alpha-like and a non-alpha-subunit recognize the same high-affinity alpha-bungarotoxin binding complex. 191 73

Nicotinic acetylcholine receptors (nAChRs) display marked heterogeneity in both vertebrates and invertebrates. Here we describe the structure of a cDNA from Drosophila melanogaster which encodes a novel nAChR beta-type subunit (SBD or beta 2). The deduced amino acid sequence of SBD displays remarkable similarity to the Drosophila alpha-subunits, ALS and SAD, while homology to the Drosophila beta-subunit ARD is less pronounced. The temporal expression of sbd transcripts during Drosophila development is similar to that of other nAChR subunit mRNAs, with high levels being found during late embryonic and late pupal stages. In embryos, sbd and als transcripts are localized in the central nervous system. The sbd gene maps cytogenetically in proximity to the als and sad genes at position 96A of chromosome 3R, suggesting the existence of a nAChR gene cluster in invertebrates.
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PMID:SBD, a novel structural subunit of the Drosophila nicotinic acetylcholine receptor, shares its genomic localization with two alpha-subunits. 212 39

The D alpha 2 gene encodes a ligand-binding subunit of nicotinic acetylcholine receptors (nAChRs) from Drosophila melanogaster. We have studied the distribution of D alpha 2 transcripts and protein by in situ hybridization and immunohistochemistry, respectively, as well as the regulation of D alpha 2 gene expression in vivo using D alpha 2 promoter fragments fused to the Escherichia coli lacZ gene. Transcripts and protein from the D alpha 2 gene were detected exclusively in the central nervous system. Both in late embryos and adults D alpha 2-like immunoreactivity is widely but not uniformly distributed in the synaptic neuropil, suggesting that the D alpha 2 protein is a subunit of a synaptic nicotinic receptor. Its distribution resembles that of ALS and ARD proteins, two other nAChR subunits of the fly. Five different D alpha 2-lacZ fusion gene constructs were introduced into the Drosophila genome by P-element-mediated gene transfer to identity functional elements of the D alpha 2 promoter. All constructs produce a basic lacZ expression pattern that is compatible with the distribution of D alpha 2 transcripts and protein. A 880 bp upstream fragment harbors the cis elements for the expression of a weak but specific basic D alpha 2 pattern. The next 350 bp further upstream significantly enhance beta-galactosidase expression without influencing the pattern of expression. Between 1.7 and 7.3 kb upstream of the transcription start site one or more elements that are required for D alpha 2 expression in optic lobe tangential cells are located.
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PMID:Expression of the ligand-binding nicotinic acetylcholine receptor subunit D alpha 2 in the Drosophila central nervous system. 786 Nov 14

Three cDNAs (ALS, D alpha 2 and ARD) isolated from the nervous system of Drosophila and encoding putative nicotinic acetylcholine receptor subunits were expressed in Xenopus oocytes in order to study their functional properties. Functional receptors could not be reconstituted from any of these subunits taken singly or in twos and threes. In contrast, large evoked currents (in the microA range) were consistently observed upon agonist application on oocytes co-injected with ALS or D alpha 2 in combination with the chick beta 2 structural subunit. The ALS/beta 2 and D alpha 2/beta 2 receptors are highly sensitive to acetylcholine and nicotine, and their physiological properties resemble those of native or reconstituted receptors from vertebrates. Although the physiological properties of ALS/beta 2 and D alpha 2/beta 2 receptors are quite similar, clear differences appear in their pharmacological profiles. The ALS/beta 2 receptor is highly sensitive to alpha-bungarotoxin while the D alpha 2/beta 2 receptor is totally insensitive to this agent. These results demonstrate that the Drosophila ALS and D alpha 2 cDNAs encode neuronal nicotinic subunits responding to physiological concentrations of the agonists acetylcholine and nicotine.
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PMID:Physiological properties of neuronal nicotinic receptors reconstituted from the vertebrate beta 2 subunit and Drosophila alpha subunits. 807 28

The distribution of two subunits of nicotinic acetylcholine receptors in the developing and the differentiated central nervous system of Drosophila melanogaster was studied. With subunit-specific antibodies raised against the ligand-binding alpha-like subunit ALS and the putative non-ligand-binding subunit ARD, we find both ALS-like and ARD-like immunoreactivity widely distributed in most neuropiles of the optic lobes, the protocerebrum, the deutocerebrum and the thoracic ganglion of the adult fly. With a single exception, namely in the lamina of the visual system, the antigens recognized by the two types of antibodies are colocalized. This observation is consistent with previous immunoprecipitation data indicating that the ALS and ARD proteins are integral components of the same hetero-oligomeric receptor that binds the nicotinic antagonist alpha-bungarotoxin with high affinity. During embryonic development ARD-like immunoreactivity is first detectable in approximately 10 hour old embryos. Both subunits are consistently detected in the central nervous system of the late embryo, the three larval stages, and all prepupal and pupal stages. During metamorphosis the optic stalk is transiently immunoreactive with anti-ARD, but not with anti-ALS antiserum. Although in larvae and adults, immunoreactivity with both types of antibodies is most abundant in synaptic regions, in embryos and pupae strong staining of cortical cell body layers is observed, in particular with anti-ARD antisera. As these developmental periods coincide with strong accumulation of ARD transcripts, the cell body staining may reflect newly synthesized and assembled receptors, while the functional ARD- and ALS-containing receptor may be destined for synapses.
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PMID:Immunohistochemical localization of a ligand-binding and a structural subunit of nicotinic acetylcholine receptors in the central nervous system of Drosophila melanogaster. 822 11

The second beta-like subunit (SBD) is a putative structural subunit of Drosophila melanogaster nicotinic acetylcholine receptors (nAChRs). Here we have produced specific antibodies against SBD to study, which other nAChR subunits can co-assemble with SBD in receptor complexes of the Drosophila nervous system. Immunohistochemical studies in the adult optic lobe revealed that SBD has a distribution similar to that of the alpha-subunit ALS in the synaptic neuropil. The subunits ALS, D(alpha)2 and SBD can be co-purified by alpha-bungarotoxin affinity chromatography. Moreover, anti-SBD antibodies co-precipitate ALS and D(alpha)2 and, vice versa, ALS and D(alpha)2 antibodies co-immunoprecipitate SBD protein. Two-step immunoaffinity chromatography with immobilized antibodies against ALS and D(alpha)2 revealed the existence of nAChR complexes that include ALS, D(alpha)2 and SBD as integral components. Interestingly, the genes encoding these three subunits appear to be directly linked in the Drosophila genome at region 96 A of the third chromosome. In addition, SBD appears to be a component of a different receptor complex, which includes the ARD protein as an additional beta-subunit, but neither ALS nor D(alpha)2 nor the third alpha-subunit D(alpha)3. These findings suggest a considerable complexity of the Drosophila nicotinic receptor system.
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PMID:Nicotinic acetylcholine receptors of Drosophila: three subunits encoded by genomically linked genes can co-assemble into the same receptor complex. 1179 53

Herein, we present the synthesis of mono-dispersed C-QDs via single-step thermal decomposition process using the fennel seeds (Foeniculum vulgare). As synthesized C-QDs have excellent colloidal, photo-stability, environmental stability (pH) and do not require any additional surface passivation step to improve the fluorescence. The C-QDs show excellent PL activity and excitation-independent emission. Synthesis of excitation-independent C-QDs, to the best of our knowledge, using natural carbon source via pyrolysis process has never been achieved before. The effect of reaction time and temperature on pyrolysis provides insight into the synthesis of C-QDs. We used Machine-learning techniques (ML) such as PCA, MCR-ALS, and NMF-ARD-SO in order to provide a plausible explanation for the origin of the PL mechanism of as-synthesized C-QDs. ML techniques are capable of handling and analyzing the large PL data-set, and institutively recommend the best excitation wavelength for PL analysis. Mono-disperse C-QDs are highly desirable and have a range of potential applications in bio-sensing, cellular imaging, LED, solar cell, supercapacitor, printing, and sensors.
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PMID:Synthesis and characterization of Mono-disperse Carbon Quantum Dots from Fennel Seeds: Photoluminescence analysis using Machine Learning. 3157 Jul 39