BDNF is induced by wild-type alpha-synuclein but not by the two mutants, A30P or A53T, in glioma cell line.
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.
Kohno
Ryuichi
R
Department of Neurology, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawaharacho, Sakyoku, Kyoto 606-8507, Japan.
Sawada
Hideyuki
H
Kawamoto
Yasuhiro
Y
Uemura
Kengo
K
Shibasaki
Hiroshi
H
Shimohama
Shun
S
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
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