Abstract
Parkinson's disease (PD) is one of the most prevalent neurodegenerative diseases but its etiology is unclear. Alpha-synuclein (alpha-SN) is a major component of Lewy bodies and Lewy neurites, and its missense mutations, A30P and A53T, cause familial PD. In PD, alpha-SN-positive glial inclusions are distributed mainly in the dorso-medial region of the substantia nigra, which contains most of the surviving dopaminergic neurons, suggesting that alpha-SN expression might have a neuroprotective function in glial cells. To investigate this hypothesis, we established alpha-SN transfected C6 glioma cell line clones and evaluated the expression of neurotrophins using semi-quantitative reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay. Brain-derived neurotrophic factor (BDNF) was induced by overexpression of wild-type alpha-SN but not by that of A30P and A53T. These data suggest that the pathogenic alpha-SN mutations, A30P or A53T, are linked to the loss of BDNF production in glial cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Substitution
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Animals
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Brain-Derived Neurotrophic Factor / antagonists & inhibitors
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Brain-Derived Neurotrophic Factor / biosynthesis*
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Calcium / chemistry
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Calcium / metabolism
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Cell Line, Tumor
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Chelating Agents / pharmacology
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Clone Cells
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Dactinomycin / pharmacology
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Egtazic Acid / analogs & derivatives*
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Egtazic Acid / pharmacology
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Glioma / metabolism*
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Humans
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Immunoblotting
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Immunohistochemistry
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Lac Operon
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Nerve Growth Factor / biosynthesis
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism
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Nerve Tissue Proteins / physiology*
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Protein Synthesis Inhibitors / pharmacology
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RNA, Messenger / biosynthesis
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Rats
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Synucleins
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Thapsigargin / pharmacology
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Transfection
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alpha-Synuclein
Substances
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Brain-Derived Neurotrophic Factor
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Chelating Agents
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Nerve Tissue Proteins
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Protein Synthesis Inhibitors
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RNA, Messenger
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Recombinant Proteins
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SNCA protein, human
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Snca protein, rat
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Synucleins
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alpha-Synuclein
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1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester
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Dactinomycin
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Egtazic Acid
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Thapsigargin
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Nerve Growth Factor
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Calcium