Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous findings suggest that the antioxidant-iron chelator green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) may have a neurorescue impact in aging and neurodegenerative diseases to retard or even reverse the accelerated rate of neuronal degeneration. The present study sought a deeper elucidation of the molecular neurorescue activity of EGCG in a progressive neurotoxic model of long-term serum deprivation of human SH-SY5Y neuroblastoma cells. In this model, proteomic analysis revealed that EGCG (0.1-1 microM) affected the expression levels of diverse proteins, including proteins related to cytoskeletal components, metabolism, heat shock, and binding. EGCG induced the levels of cytoskeletal proteins, such as beta tubulin IV and tropomyosin 3, playing a role in facilitating cell assembly. In accordance, EGCG increased the levels of the binding protein 14-3-3 gamma, involved in cytoskeletal regulation and signal transduction pathways in neurons. Additionally, EGCG decreased protein levels and mRNA expression of the beta subunit of the enzyme prolyl 4-hydroxylase, which belongs to a family of iron-oxygen sensors of hypoxia-inducible factor (HIF) prolyl hydroxylases that negatively regulate the stability and degradation of several proteins involved in cell survival and differentiation. Accordingly, EGCG decreased protein levels of two molecular chaperones that were associated with HIF regulation, the immunoglobulin-heavy-chain binding protein and the heat shock protein 90 beta. Thus, the present study sheds some light on the antioxidative-iron chelating activities of EGCG underlying its neuroprotective/neurorescue mechanism of action, further suggesting a potential neurodegenerative-modifying effect for EGCG.
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PMID:A novel approach of proteomics and transcriptomics to study the mechanism of action of the antioxidant-iron chelator green tea polyphenol (-)-epigallocatechin-3-gallate. 1764 May 65

The anaplastic lymphoma kinase gene (ALK) is a gene on chromosome 2p23 that has expression restricted to the brain, testis and small intestine but is not expressed in normal lymphoid tissue. It has similarity to the insulin receptor subfamily of kinases and is emerging as having increased pathologic and potential therapeutic importance in malignant disease. This gene was originally established as being implicated in the pathogenesis of rare diseases including inflammatory myofibroblastic tumour (IMT) and ALK-positive anaplastic large cell lymphoma, which is a subtype of non-Hodgkin's lymphoma. Recently the number of diseases in which ALK is implicated in their pathogenesis has increased. In 2007, an inversion of chromosome 2 involving ALK and a fusion partner gene in a subset of non-small cell lung cancer was discovered. In 2008, publications emerged implicating ALK in familial and sporadic cases of neuroblastoma, a childhood cancer of the sympatho-adrenal system. Chromosomal abnormalities involving ALK are translocations, amplifications or mutations. Chromosomal translocations are the longest recognised ALK genetic abnormality. When translocations occur a fusion gene is created between ALK and a gene partner. This has been described in ALK-positive anaplastic large cell lymphoma in which ALK is fused to NPM (nucleolar protein gene) and in non-small cell lung cancer where ALK is fused to EML4 (Echinoderm microtubule-associated protein 4). The most frequently described partner genes in inflammatory myofibroblastic tumour are tropomyosin 3/4 (TMP3/4), however in IMTs a diversity of ALK fusion partners have been found, with the ability to homodimerise a common characteristic. Point mutations and amplification of the ALK gene occur in the childhood cancer neuroblastoma. Therapeutic targeting of ALK fusion genes using tyrosine kinase inhibition, vaccination using an ALK specific antigen and treatment using viral vectors for RNAi are emerging potential therapeutic possibilities.
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PMID:The emerging pathogenic and therapeutic importance of the anaplastic lymphoma kinase gene. 2045 71