Phosphorylation of alpha-synuclein characteristic of synucleinopathy lesions is recapitulated in alpha-synuclein transgenic Drosophila

Neurosci Lett. 2003 Jan 23;336(3):155-8. doi: 10.1016/s0304-3940(02)01258-2.

Abstract

alpha-Synuclein is a major component of Lewy bodies in the brains of patients with Parkinson's disease (PD) as well as of neuronal/glial inclusions in a subset of neurodegenerative disorders collectively termed synucleinopathies. Here we studied by immunohistochemistry the accumulation of alpha-synuclein in transgenic (TG) Drosophila overexpressing wild-type (WT) or familial PD-linked mutant (i.e. A30P and A53T) alpha-synuclein in neurons, with special reference to the phosphorylation at Ser129, that is characteristic of human synucleinopathy lesions. Progressive accumulation of human alpha-synuclein was widely observed in the cell bodies and neurites of major neuronal nuclei in TG Drosophila brains, and phosphorylation of alpha-synuclein at Ser129 was detected in a limited subset of neurons approximately 1 week after alpha-synuclein immunoreactivity was first detected. Phosphorylated alpha-synuclein was most abundant in A53T mutant, followed by A30P and WT Drosophila. These results suggest that accumulation and phosphorylation of alpha-synuclein is recapitulated in neurons of alpha-synuclein transgenic Drosophila, that underscores the relevance of this model to human synucleinopatheis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drosophila
  • Immunohistochemistry
  • Mutation*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neurodegenerative Diseases / metabolism*
  • Neurons / metabolism*
  • Phosphorylation
  • Serine / metabolism
  • Synucleins
  • Time Factors
  • alpha-Synuclein

Substances

  • Nerve Tissue Proteins
  • Synucleins
  • alpha-Synuclein
  • Serine