Biology Reference
In-Depth Information
ABSTRACT
Parkinson's disease (PD) is the second most prevalent neurodegenerative disor-
der principally affecting the dopaminergic neurons of the substantia nigra. The
pathogenic mechanisms are unknown and there are currently no cure or disease-
modifying therapies. Recent genetic linkage studies have begun to identify
single-gene mutations responsible for rare heritable forms of PD and define
genetic risk factors contributing to disease prevalence in sporadic cases. These
findings provide an opportunity to gain insight into the molecular mechanisms of
this disorder through the creation and analysis of appropriate genetic models.
One model system that has proven surprisingly tractable for these studies is the
fruit fly,
. Analysis of a number of Drosophila models of
PD has revealed some profound and sometimes surprising insights into PD
pathogenesis. Moreover, these models can be used to investigate potential
therapeutic strategies that may be effective
Drosophila melanogaster
, and tests have highlighted
the efficacy of a number of neuroprotective compounds. Here, I review the
methodologies employed in developing the various Drosophila models, and the
recent advances that these models in particular have contributed to our under-
standing of the mechanisms that underlie PD pathogenesis and possible treat-
ment strategies.
in vivo
2011, Elsevier Inc.
I. INTRODUCTION
Neurodegenerative diseases such as Parkinson's, Alzheimer's, and motor neuron
diseases will be a considerable medical challenge in the twenty first century, due
to their extremely debilitating effects and because of a profound lack of effective
therapies that replace dead or dying neurons. Another plausible therapeutic
approach is to develop disease-modifying treatments that halt or reverse neuro-
nal deterioration before they are lost. For this method to be realistic, another
major challenge must be overcome, that of identifying early stage or presympto-
matic patients who still retain some intact neuronal architecture. While consid-
erable advances are being made in the identification of prodrome biomarkers,
effective therapies to halt neurodegeneration remain to be developed. This is
itself held back by our lack of understanding into the causes of neurodegenerative
diseases. Hence, a more complete insight into the pathogenic mechanisms
represents
the first
link in the chain of developments
toward effective
therapeutics.
Parkinson's disease (PD) is the most common neurodegenerative move-
ment disorder, affecting approximately 1% of the retirement-age population.
There are currently no cures and no effective disease-modifying therapies. It is
not only typically recognized by the classic motor system disturbances such as
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