Biology Reference
In-Depth Information
Modeling diseases in simple invertebrate systems is attractive because genet-
ics can define cellular cascades mediating disease states such as the death of
neurons in Parkinson's disease, the second most common neurodegenerative
disorder in humans (
Feany and Bender 2000
). Transgenic
Drosophila
containing
a mutant form of the human
α
-synuclein gene exhibit the essential features of
the Parkinson's disease in humans, making it possible to study the function of
α
-synuclein and determine the underlying pathogenic mechanisms in a geneti-
cally tractable animal.
The
spongecake
mutant of
Drosophila
shows degenerative changes similar to
that seen in humans with Creutzfeldt-Jakob disease, while the
eggroll
mutant
produces changes similar to those seen in humans with Tay-Sachs disease (
Min
and Benzer 1997
). The
beta-
a
myloid
p
rotein
p
recursor-
l
ike
(
Appl
) gene of
Drosophila
encodes a homolog of the human
β
-amyloid precursor protein which
gives rise to
β
-amyloid, a major component of the plaques found in patients suf-
fering from Alzheimer's disease (
Luo et al. 1992
). Another protein associated
with Alzheimer's disease, presenilin, has been found in
Drosophila
and studies
suggest it also may be involved in the development of the pathology (
Fortini
and Bonini 2000
). A
Drosophila
homolog was identified for the human gene
for copper/zinc superoxide dismutase; mutants of this gene are implicated in
Lou Gehrig's disease (
McCabe 1995, Phillips et al. 1995
).
A recessive mutant (
bubblegum
) in
D. melanogaster
exhibits adult neurode-
generation similar to that seen in the human disease adrenoleukodystrophy
(ALD), otherwise known as the disease cured in the movie
Lorenzo's Oil
(
Min
and Benzer 1999
). In ALD, high levels of very long chain fatty acids are pro-
duced that can be lowered by dietary treatment with a mixture of unsaturated
fatty acids; feeding the ALD flies one of the components, glyceryl trioleate oil,
blocked the accumulation of excess very long chain fatty acids and eliminated
the pathology. Thus,
bubblegum
flies provide a model system for studying
mechanisms of disease and screening drugs for treatment.
Drosophila
may serve as a model organism to study the genetics of alcohol
abuse and drug addiction in humans (
Bellen 1998, Moore et al. 1998, Andretic
et al. 1999, Wolf 1999, Bainton et al. 2000, Singh and Heberlein 2000
). Alcohol
addiction and many types of drug addictions appear to share common mecha-
nisms (
Bellen 1998, Moore et al. 1998
). For example, the “dopamine hypothe-
sis” suggests that addictive drugs may activate certain areas of the human brain
leading to an increase in dopamine neurotransmitter release (
Bainton et al.
2000
). Elevation of dopamine probably provides a sense of wellbeing, plea-
sure, or elation resulting in a positive reinforcement. Dopamine is not the only
