Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Accumulating evidence suggests that extracellular alpha-synuclein (eSNCA) plays an important role in the pathogenesis of Parkinson's disease or related synucleinopathies by inducing neurotoxicity directly or indirectly via microglial or astroglial activation. However, the mechanisms by which this occurs remain to be characterized. To explore these mechanisms, we combined three biochemical techniques - stable isotope labeling of amino acid in cell cultures (SILAC), biotin labeling of plasma membrane proteins followed by affinity purification, and analysis of unique proteins binding to SNCA peptides on membrane arrays. The SILAC proteomic analysis identified 457 proteins, of which, 245 or 172 proteins belonged to membrane or membrane associated proteins, depending on the various bioinformatics tools used for interpretation. In dopamine neuronal cells treated with eSNCA, the levels of 86 membrane proteins were increased and 35 were decreased compared with untreated cells. In peptide array analysis, 127 proteins were identified as possibly interacting with eSNCA. Of those, seven proteins were overlapped with the membrane proteins that displayed alterations in relative abundance after eSNCA treatment. One was ciliary neurotrophic factor receptor, which appeared to modulate eSNCA-mediated neurotoxicity via mechanisms related to JAK1/STAT3 signaling but independent of eSNCA endocytosis.
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PMID:Identification of ciliary neurotrophic factor receptor alpha as a mediator of neurotoxicity induced by alpha-synuclein. 2034 Jan 60

Oxidative stress is an important cause of cellular toxicity in the central nervous system and contributes to the pathology associated with neurodegenerative disorders including Parkinson's disease. As such, elucidation of cellular mechanisms that enhance neuronal resistance to oxidative stress may provide new avenues for therapy. In this study we employed a simple two-state cellular model to identify genes that are associated with resistance to oxidative stress induced by 6-hydroxydopamine (6-OHDA). In this model, undifferentiated neuroblastoma cells display higher sensitivity to 6-OHDA than differentiated cells. By comparing the gene expression between these two states, we identified several genes whose expression is altered concomitant with changes in 6-OHDA sensitivity. This gene set includes cytokine receptor-like factor 1 (CRLF1), which is up-regulated during the differentiation process and has been previously implicated in neuroprotection. We show that the product of this gene is both necessary and sufficient for increased resistance to 6-OHDA in differentiated neuroblastoma cells, and that CRLF1 serves its protective role by a cell autonomous mechanism that is independent from its known role as a co-ligand for the ciliary neurotrophic factor receptor. These data provide an additional role for CRLF1 that could potentially explain its broad expression pattern and effects on cells lacking expression of this receptor.
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PMID:Cytokine receptor-like factor 1 (CRLF1) protects against 6-hydroxydopamine toxicity independent of the gp130/JAK signaling pathway. 2381 41