title: BDNF is induced by wild-type alpha-synuclein but not by the two mutants, A30P or A53T, in glioma cell line.
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.
authors.affiliation: Department of Neurology, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawaharacho, Sakyoku, Kyoto 606-8507, Japan.
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Kohno
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Sawada
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kawamoto
authors.forename: Kengo
authors.initials: K
authors.lastname: Uemura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shibasaki
authors.forename: Shun
authors.initials: S
authors.lastname: Shimohama
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D002118:Calcium / Q000737:chemistry / Q000378:metabolism; D045744:Cell Line, Tumor; D002614:Chelating Agents / Q000494:pharmacology; D002999:Clone Cells; D003609:Dactinomycin / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D005910:Glioma / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D007763:Lac Operon; D020932:Nerve Growth Factor / Q000096:biosynthesis; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D051843:Synucleins; D019284:Thapsigargin / Q000494:pharmacology; D014162:Transfection; D051844:alpha-Synuclein
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D002614:Chelating Agents; D009419:Nerve Tissue Proteins; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D011994:Recombinant Proteins; C497604:SNCA protein, human; C497606:Snca protein, rat; D051843:Synucleins; D051844:alpha-Synuclein; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D003609:Dactinomycin; D004533:Egtazic Acid; D019284:Thapsigargin; D020932:Nerve Growth Factor; D002118:Calcium