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 ALS gene family of Candida albicans consists of eight genes (ALS1 to ALS7 and ALS9) that encode cell-wall glycoproteins involved in adhesion to host surfaces. Considerable allelic sequence variability has been documented for regions of ALS genes encoding repeated sequences. Although regions of ALS genes encoding non-repeated sequences tend to be more conserved, some sequence divergence has been noted, particularly for alleles of ALS5. Data from the C. albicans genome sequencing project provided the first indication that strain SC5314 encoded two divergent ALS9-like sequences and that three of the ALS genes (ALS5, ALS1 and ALS9) were contiguous on chromosome 6. Data from PCR analysis and construction of both single and double deletion mutants indicated that the divergent sequences were alleles of ALS9, and located downstream of ALS5 and ALS1. Sequences within the 5' domain of ALS9-1 and ALS9-2 varied by 11 %. Within the 3' domain of each allele, extra nucleotides were present in two regions of ALS9-2, designated Variable Block 1 (VB1) and Variable Block 2 (VB2). Analysis of strains from the five major C. albicans genetic clades showed that both ALS9 alleles are widespread among these strains, that the sequences of ALS9-1 and ALS9-2 are conserved among diverse strains and that recombinant ALS9 alleles have been generated during C. albicans evolution. Phylogenetic analysis showed that, although divergent in sequence, ALS9 alleles are more similar to each other than to any other ALS genes. The degree of sequence divergence for ALS9 greatly exceeds that observed previously for other ALS genes and may result in functional differences for the proteins encoded by the two alleles.
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PMID:Allelic variation in the contiguous loci encoding Candida albicans ALS5, ALS1 and ALS9. 1452 27

An RT-PCR assay was developed to analyse expression patterns of genes in the Candida albicans ALS (agglutinin-like sequence) family. Inoculation of a reconstituted human buccal epithelium (RHE) model of mucocutaneous candidiasis with strain SC5314 showed destruction of the epithelial layer by C. albicans and also formation of an upper fungal layer that had characteristics similar to a biofilm. RT-PCR analysis of total RNA samples extracted from C. albicans-inoculated buccal RHE showed that ALS1, ALS2, ALS3, ALS4, ALS5 and ALS9 were consistently detected over time as destruction of the RHE progressed. Detection of transcripts from ALS7, and particularly from ALS6, was more sporadic, but not associated with a strictly temporal pattern. The expression pattern of ALS genes in C. albicans cultures used to inoculate the RHE was similar to that observed in the RHE model, suggesting that contact of C. albicans with buccal RHE does little to alter ALS gene expression. RT-PCR analysis of RNA samples extracted from model denture and catheter biofilms showed similar gene expression patterns to the buccal RHE specimens. Results from the RT-PCR analysis of biofilm RNA specimens were consistent between various C. albicans strains during biofilm development and were comparable to gene expression patterns in planktonic cells. The RT-PCR assay described here will be useful for analysis of human clinical specimens and samples from other disease models. The method will provide further insight into the role of ALS genes and their encoded proteins in the diverse interactions between C. albicans and its host.
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PMID:RT-PCR detection of Candida albicans ALS gene expression in the reconstituted human epithelium (RHE) model of oral candidiasis and in model biofilms. 1476 4

Sequence variations with biologic effect in ALS have been identified in the gene for vascular endothelial growth factor (VEGF). The gene for a related protein, angiogenin, lies on chromosome 14q11.2. Analysis of the angiogenin (ANG) gene in the authors' population has demonstrated a significant allelic association with the rs11701 single nucleotide polymorphism (SNP) and identified a novel mutation in two individuals with sporadic ALS that potentially inhibits angiogenin function. These observations propose a candidate region for ALS on chromosome 14q11.2 and suggest that other genes with similar function to VEGF may be important in the pathogenesis of ALS.
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PMID:A novel candidate region for ALS on chromosome 14q11.2. 1555 16

Candida albicans PALS-green fluorescent protein (GFP) reporter strains were inoculated into mice in a disseminated candidiasis model, and GFP production was monitored by immunohistochemistry and reverse transcription-PCR (RT-PCR). GFP production from the ALS1 and ALS3 promoters was detected immunohistochemically. ALS1, ALS2, ALS3, ALS4, and ALS9 transcription was detected by RT-PCR, further identifying ALS genes expressed in this model.
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PMID:Use of green fluorescent protein and reverse transcription-PCR to monitor Candida albicans agglutinin-like sequence gene expression in a murine model of disseminated candidiasis. 1573 Oct 87

The gene encoding yeast-enhanced green fluorescent protein (GFP) was placed under control of ALS gene promoters in Candida albicans. The PALS-GFP reporter strains were validated using various techniques including a new real-time RT-PCR assay to quantify ALS gene expression. The PALS-GFP reporter strains were grown in media that promoted yeast or germ tube forms, and the resulting fluorescence was measured by flow cytometry. In addition to results that indicate differences in ALS gene expression due to growth medium, growth stage and developmental programme, new data show large differences in transcriptional level among the ALS genes. Expression of ALS1 was associated with transfer of the PALS1-GFP strain to fresh growth medium. ALS3 expression increased markedly when germ tubes were visible microscopically and ALS7 expression exhibited a transient peak between 2 and 3 h following inoculation into fresh YPD medium. Transcription from the ALS1 and ALS3 promoters was strongest among those tested and contrasted markedly with the weaker promoter strength at the ALS5, ALS6, ALS7 and ALS9 loci. These weaker transcriptional responses were also observed using real-time RT-PCR measurements on wild-type C. albicans cells. Assuming a positive correlation between transcriptional level and protein production, these results suggest that some Als proteins are abundant on the C. albicans cell surface while others are produced at a much lower level.
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PMID:Construction and real-time RT-PCR validation of Candida albicans PALS-GFP reporter strains and their use in flow cytometry analysis of ALS gene expression in budding and filamenting cells. 1581 74

We recently identified angiogenin (ANG) as a candidate susceptibility gene for amyotrophic lateral sclerosis (ALS), a neurodegenerative disorder characterized by adult-onset loss of motor neurons. We now report the finding of seven missense mutations in 15 individuals, of whom four had familial ALS and 11 apparently 'sporadic' ALS. Our findings provide further evidence that variations in hypoxia-inducible genes have an important role in motor neuron degeneration.
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PMID:ANG mutations segregate with familial and 'sporadic' amyotrophic lateral sclerosis. 1650 76

ALS gene expression was studied in the hyposalivatory rat model of oral candidiasis and in clinical specimens collected from HIV-positive patients to assess similarities in expression patterns between the model system and clinical isolates. Two Candida albicans strains, SC5314 and OY-2-76, were used in the rat model system and infection progressed for 3 or 5 days. The strains produced similar oral lesions at 3 days. At 5 days, strain OY-2-76 produced more superficial lesions containing relatively more yeast forms compared to invasive hyphal forms observed for strain SC5314. For all infections, the most severe lesions were observed on the tongue and gingiva overlying the mandible. ALS transcripts were easier to detect by RT-PCR later in infection and under other conditions where more fungal cells were present. Expression of ALS1, ALS2, ALS3 and ALS4 was observed in rats infected for 3 days with ALS5 and ALS9 transcripts detected after 5 days of infection. Expression of ALS6 was observed in a single specimen from a 5-day infection while ALS7 transcript was never found. Expression of all ALS genes was observed in oral clinical material collected from HIV-positive patients although ALS6 and ALS7 transcripts required an extra PCR amplification step to be detected. Overall, the patterns of ALS gene expression were similar between the rat model and human clinical specimens, suggesting that the model would be useful for studying the phenotype of al delta/al delta mutant strains.
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PMID:RT-PCR analysis of Candida albicans ALS gene expression in a hyposalivatory rat model of oral candidiasis and in HIV-positive human patients. 1651 12

Although amyotrophic lateral sclerosis (ALS) was described more than 130 years ago, the cause(s) of most cases of this adult motor neuron disease remains a mystery. With the discovery of mutations in one gene (Cu/Zn superoxide dismutase) as a primary cause of some forms of ALS, model systems have been developed that have helped us begin to understand mechanisms involved in motor neuron death and enabled testing of potential new therapies. Several other genes have been implicated as risk factors in motor neuron diseases, including neurofilaments, cytoplasmic dynein and dynactin, vascular endothelial growth factor, and angiogenin. With advances in the basic research of the disease, many hypotheses accounting for motor neuron death are being explored, including loss of trophic support, protein mishandling, mitochondrial dysfunction, excitotoxicity, axonal abnormalities and inflammation. Many of these mechanisms are the focus of research in other neurodegenerative disorders, such as Parkinson's, Alzheimer's and Huntington's disease.
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PMID:Therapeutic targets for amyotrophic lateral sclerosis: current treatments and prospects for more effective therapies. 1653 45

A new study by Greenway and colleagues links mutations in the angiogenin gene to patients with amyotrophic lateral sclerosis (ALS)--a progressive and fatal motoneuron disease. This is an unexpected finding because angiogenin was originally identified as a molecule involved in the formation of blood vessels (angiogenesis). Angiogenin bears striking similarity to vascular endothelial growth factor (VEGF), which is the prototypic angiogenic factor that has recently emerged as a molecule with important neuroprotective activities. Besides VEGF, angiogenin is the second so-called angiogenic factor implicated in ALS, raising the question of whether additional angiogenic factors might have a role in ALS. Overall, these findings identify angiogenin as a novel candidate gene in the pathogenesis of ALS--a discovery that ultimately might lead to the development of new therapeutic strategies.
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PMID:Another angiogenic gene linked to amyotrophic lateral sclerosis. 1684 25

To investigate the role of vascular endothelial growth factor (VEGF) and angiogenin (ANG) as genetic determinants in the susceptibility to sporadic ALS in Italian patients. VEGF genotype and haplotype analysis revealed no association between any variants and the risk of ALS. Regarding ANG gene, no mutation was detected and the rs11701 polymorphism, previously described as associated with ALS, was not differently distributed between patients and controls. Overall, our data argue against the hypothesis of both genes as risk factors for motoneuron neurodegeneration, at least in an Italian population.
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PMID:Absence of angiogenic genes modification in Italian ALS patients. 1711 98


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