Prion-like acceleration of a synucleinopathy in a transgenic mouse model

Neurobiol Aging. 2012 Sep;33(9):2225-8. doi: 10.1016/j.neurobiolaging.2011.06.022. Epub 2011 Aug 3.


Our aim in this study was to investigate experimentally the possible in vivo transmission of a synucleinopathy, using a transgenic mouse model (TgM83) expressing the human A53T mutated α-synuclein. Brain homogenates from old TgM83 mice showing motor clinical signs due to the synucleinopathy and containing insoluble and phosphorylated (pSer129) α-synuclein were intracerebrally inoculated in young TgM83 mice. This triggered an early onset of characteristic motor clinical signs, compared with uninoculated TgM83 mice or to mice inoculated with a brain homogenate from a young, healthy TgM83 mouse. This early disease was associated with insoluble α-synuclein phosphorylated on Ser129, as already identified in old and sick uninoculated TgM83 transgenic mice. Although the molecular mechanisms remain to be determined, acceleration of the pathology following inoculation of mice expressing human mutated α-synuclein with tissues from mice affected by the synucleinopathy, could be consistent with "prion-like" propagation of the disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Disease Models, Animal
  • Humans
  • Intermediate Filament Proteins / genetics*
  • Intermediate Filament Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Movement Disorders / etiology
  • Movement Disorders / genetics
  • Mutation / genetics*
  • Phosphorylation / genetics
  • Prion Diseases / complications
  • Prion Diseases / genetics*
  • Prion Diseases / metabolism*
  • Prion Diseases / mortality
  • Serine / genetics
  • Survival Analysis


  • Intermediate Filament Proteins
  • desmuslin
  • Serine