Biology Reference
In-Depth Information
These observations on the consistency in nematode nervous system
structure between species hold firm to this day and continue to under-
score the value of the baseline physiology and pharmacology work on
Ascaris to the broader understanding of nematode neurobiology and
behavior. Despite having diverged in the order of 500 million years ago,
10
the nervous systems of Ascaris and C. elegans are recognized as virtual
scale models of each other.
11
Considering the evolutionary distance
between them, this structural conservation is remarkable.
Onequirkofnematodeparasitecontrolisthepredominanceof
chemotherapeutics which act to disrupt normal neuromuscular func-
tion. In spite of the fact that all front-line anthelmintics were discovered
empirically, the vast majority have mechanisms of action that center on
the dysregulation of normal parasite behavior through the impairment
of normal coordinated neuromuscular function.
12
This is most apparent
in nematodes whereby drugs such as derquantel, emodepside, leva-
misole, the macrocyclic lactones, monepantel, piperazine, and pyrantel
cause paralysis, reducing parasite ability to survive within the
host.
13
e
19
Thefactthatmanyoftheseagentshavebroad-spectrum
activities across diverse nematode species illustrates the widespread
conservation of neuromuscular signaling components, suggesting that
functional similarities echo the structural similarities of nematode
nervous systems noted by the pioneers of nematode neurobiology.
A. suum is now well established as a model species for the pharmaco-
logical/physiological
interrogation of anthelmintic mechanisms of
action.
13,20
e
24
Since neuromuscular function emerged independently as a useful
target resource from the empirical screening programs that identified
these drugs in the first place, it holds candidature as the prima facie
resource for targets for chemotherapeutic interventions in helminth
parasites.
12,25
The portfolio of anthelmintic targets sourced from nema-
tode neuromuscular signaling systems is a component of a relatively
small number of classical signaling pathways (e.g. acetylcholine, gluta-
mate,
g
-aminobutyric acid). This encourages the view that other
exploitable parasite control targets involved in distinct signaling path-
ways associated with neuromuscular function await discovery and
provide impetus for research on the neurobiology of these organisms.
26,27
Already established as a key model species for the interrogation of
nematode parasite physiology/pharmacology, the publication of the
A. suum genome sequence has added to its appeal as a model system for
nematode research (see Chapter 11).
28
Indeed, these new data elevate
Ascaris from a surrogate model for physiology/pharmacology studies in
nematodes to a tool for discovery biology and candidate target validation.
While there are many aspects of neural function yet to be understood in
Ascaris, some of the outstanding issues will be emphasized here.
