BDNF is induced by wild-type alpha-synuclein but not by the two mutants, A30P or A53T, in glioma cell line

Biochem Biophys Res Commun. 2004 May 21;318(1):113-8. doi: 10.1016/j.bbrc.2004.04.012.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution
  • Animals
  • Brain-Derived Neurotrophic Factor / antagonists & inhibitors
  • Brain-Derived Neurotrophic Factor / biosynthesis*
  • Calcium / chemistry
  • Calcium / metabolism
  • Cell Line, Tumor
  • Chelating Agents / pharmacology
  • Clone Cells
  • Dactinomycin / pharmacology
  • Egtazic Acid / analogs & derivatives*
  • Egtazic Acid / pharmacology
  • Glioma / metabolism*
  • Humans
  • Immunoblotting
  • Immunohistochemistry
  • Lac Operon
  • Nerve Growth Factor / biosynthesis
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Nerve Tissue Proteins / physiology*
  • Protein Synthesis Inhibitors / pharmacology
  • RNA, Messenger / biosynthesis
  • Rats
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Synucleins
  • Thapsigargin / pharmacology
  • Transfection
  • alpha-Synuclein

Substances

  • Brain-Derived Neurotrophic Factor
  • Chelating Agents
  • Nerve Tissue Proteins
  • Protein Synthesis Inhibitors
  • RNA, Messenger
  • Recombinant Proteins
  • SNCA protein, human
  • Snca protein, rat
  • Synucleins
  • alpha-Synuclein
  • 1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester
  • Dactinomycin
  • Egtazic Acid
  • Thapsigargin
  • Nerve Growth Factor
  • Calcium