Why do you think your paper is highly cited?

This paper is highly cited because it describes a novel model of Parkinson’s disease (PD) that synthesizes much of what we know about the pathogenesis of the disease.  PD has been associated with environmental exposures and systemic mitochondrial dysfunction.  Pathologically, PD is characterized by the relatively selective degeneration of the nigrostriatal dopaminergic pathway and the development of cytoplasmic protein aggregates containing a-synuclein and ubiquitin.  Additionally, PD is a progressive disorder, with the symptoms becoming worse over time.  In this paper, we demonstrated that chronic, systemic exposure of rotenone, a pesticide and mitochondrial toxin, to rats reproduced many features of PD including selective nigrostriatal degeneration and a-synuclein aggregate formation.  These findings greatly enhance our understanding of the etiology of PD and provide a proof of principle that an environmental agent and mitochondrial toxin can cause parkinsonism under certain conditions.

  Does it describe a new discovery or a new methodology that's useful to others?

Yes.  Our paper describes a novel model of PD based upon chronic, systemic exposure to the mitochondrial toxin and pesticide rotenone.  Chronic rotenone exposure reproduces many features of PD.  The rotenone model can be used by others to more completely understand the etiology of PD and test hypotheses to examine the selective vulnerability of certain neuronal populations in the disease.  The rotenone model will also be useful in determining the complex interactions between environmental and genetic factors in causing PD.

  What were some of the circumstances that led you to do this research?

The pathogenesis of PD is not completely understood.  Epidemiological studies suggested an association with environmental exposures.  Biochemical studies demonstrated systemic mitochondrial dysfunction in complex I of the mitochondrial electron transport chain in many tissues of PD patients including brain, muscle, and platelets.  Based on this information, we tested the hypothesis whether systemic exposure to a mitochondrial toxin and pesticide, such as rotenone, could reproduce features of PD.

  Could you summarize the significance of your paper in layman's terms?

Our paper demonstrates that under certain conditions, features of PD can be mimicked by chronic exposure to an environmental toxin, rotenone.  Since many other environmental agents act at the same site as rotenone in mitochondria, these results provide support for a role of environmental toxins in PD pathogenesis.

Todd Sherer, Ph.D., Postdoctoral fellow
Department of Neurology, Center for Neurodegenerative Diseases
Emory University
Atlanta, GA, USA