Biology Reference
In-Depth Information
are already known as causative agents in neurodegeneration. The contributions
to the field from GWAS are still materializing; hence, the majority of insights
into pathogenesis have so far come from analysis of genes linked to rare Mende-
lian forms of PD. While the identification of these genes has tremendous
potential to provide insight into the mechanisms of PD, we do not currently
fully understand their biological functions and how their mutation results in
neuronal death. Generating animal models that recapitulate the genetic lesions
leading to disease is an essential tool on the path to fully elucidating the disease
biology. One promising approach to this problem involves the use of classical
genetic analysis in the fruit fly
to identify the genetic
pathways leading to pathology in fly models of this disease. This review describes
the features that make Drosophila useful in studies of the genes implicated in
heritable forms of PD and how these studies have begun to contribute to our
understanding of the pathogenesis of this disorder and the identification of
potential treatment strategies for PD.
Drosophila melanogaster
II. DROSOPHILA AS A MODEL ORGANISM
D. melanogaster
, commonly referred to as fruit flies reflecting their natural habitat
on rotting fruit, belong to the family Drosophilidae, which derives its name from
the Greek (
loving). Over the past century, studies of
Drosophila genetic and molecular pathways have provided pivotal advances in
our understanding of fundamental biological processes, such as chromosome
structure and segregation, regulation of gene expression, mechanisms of devel-
opment, and genetic control of behavior (Ashburner and Novitski, 1976). These
studies, together with more recent genome sequencing efforts, have made it clear
that gene sequence and gene function are highly conserved between flies and
humans (Rubin
drosos ¼
dew and
philos ¼
, 2000). This conservation has contributed enormously to
our current understanding of human biology and the pathogenesis of particular
human diseases. For example, the Drosophila counterparts to numerous tumor
suppressor and proto-oncogenes have provided a wealth of understanding about
the pathways involved in cancer. While much of the insight into human disease
mechanisms derived from genetic studies of Drosophila has been a byproduct of
investigations of more fundamental biological questions, the increasing appreci-
ation of the usefulness of Drosophila to address questions of human pathogenesis
has led more recently to overt efforts to model specific human diseases (Bier,
2005). Over the past several years, significant effort has been invested in the
development of Drosophila models of neurological diseases, such as polygluta-
mine diseases, Alzheimer's disease, PD, and others (Lessing and Bonini, 2009; Lu
and Vogel, 2009). The extensive degree of conservation of neuronal function
and development at
et al.
the cellular
level between Drosophila and higher
