Spread of neuronal degeneration in a dopaminergic, Lrrk-G2019S model of Parkinson disease

Autophagy. 2013 Jun 1;9(6):936-8. doi: 10.4161/auto.24397. Epub 2013 Mar 25.


Flies expressing the most common Parkinson disease (PD)-related mutation, LRRK2-G2019S, in their dopaminergic neurons show loss of visual function and degeneration of the retina, including mitochondrial abnormalities, apoptosis and autophagy. Since the photoreceptors that degenerate are not dopaminergic, this demonstrates nonautonomous degeneration, and a spread of pathology. This provides a model consistent with Braak's hypothesis on progressive PD. The loss of visual function is specific for the G2019S mutation, implying the cause is its increased kinase activity, and is enhanced by increased neuronal activity. These data suggest novel explanations for the variability in animal models of PD. The specificity of visual loss to G2019S, coupled with the differences in neural firing rate, provide an explanation for the variability between people with PD in visual tests.

Keywords: Drosophila; LRRK2; Parkinson disease; dopaminergic neurons; electroretinogram; neurodegeneration; photoreceptors; vision.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Disease Models, Animal
  • Dopaminergic Neurons / enzymology
  • Dopaminergic Neurons / pathology*
  • Drosophila melanogaster / genetics
  • Humans
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • Mutation / genetics*
  • Nerve Degeneration / enzymology
  • Nerve Degeneration / pathology*
  • Parkinson Disease / enzymology*
  • Parkinson Disease / pathology*
  • Protein Serine-Threonine Kinases / genetics*
  • Retinal Degeneration / enzymology
  • Retinal Degeneration / pathology


  • Adenosine Triphosphate
  • LRRK2 protein, human
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • Protein Serine-Threonine Kinases