[Abstract Title]. - Society for Neuroscience

day 26. Alpha-synuclein (α-syn), the primary protein implicated in the pathogenesis of
Parkinson‟s Disease (PD), is cleaved in vitro by CD at Tyr125, lending further evidence to the
observation that decreased protein metabolism is one possible mechanism that results in the
formation of Lewy Bodies, proteinaceous inclusions composed of α-syn and other proteins that
serve as histological hallmarks of PD. Using mice that were either wild type (WT) or
heterozygous (HET) for cd, we tested the hypothesis that cd haploinsufficiency results in greater
sensitivity to the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropryridine (MPTP). Previous
studies have demonstrated that α-syn null mice are MPTP resistant, therefore, a protease such as
CD, which is capable of metabolizing α-syn may be neuroprotective and thus a potential drug
target for PD therapy. Acute (20mg/kg X 4 injections/day X 1 day) (n=3 WT, n=3 HET) and
chronic (30mg/kg X 1 injection/day X 10 days) (n=4 WT, n=4 HET) intraperitoneal MPTP
injection protocols were tested. Fine, ambulatory and total movement was measured by photocell
beam breaks both pre- and post-MPTP injection. Total ambulatory hypolocomotor activity
showed the greatest significance at day 3 post-MPTP injection with the WT being significantly
higher than the HET after acute injection (p