Pathological α-synuclein transmission initiates Parkinson-like neurodegeneration in nontransgenic mice

  • Luk K
  • Kehm V
  • Carroll J
 et al. 
  • 779

    Readers

    Mendeley users who have this article in their library.
  • 712

    Citations

    Citations of this article.

Abstract

Parkinson's disease is characterized by abundant α-synuclein (α-Syn) neuronal inclusions, known as Lewy bodies and Lewy neurites, and the massive loss of midbrain dopamine neurons. However, a cause-and-effect relationship between Lewy inclusion formation and neurodegeneration remains unclear. Here, we found that in wild-type nontransgenic mice, a single intrastriatal inoculation of synthetic α-Syn fibrils led to the cell-to-cell transmission of pathologic α-Syn and Parkinson's-like Lewy pathology in anatomically interconnected regions. Lewy pathology accumulation resulted in progressive loss of dopamine neurons in the substantia nigra pars compacta, but not in the adjacent ventral tegmental area, and was accompanied by reduced dopamine levels culminating in motor deficits. This recapitulation of a neurodegenerative cascade thus establishes a mechanistic link between transmission of pathologic α-Syn and the cardinal features of Parkinson's disease.

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Authors

  • Kelvin C. Luk

  • Victoria Kehm

  • Jenna Carroll

  • Bin Zhang

  • Patrick O'Brien

  • John Q. Trojanowski

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free