[Abstract Title]. - Society for Neuroscience

hyperactivity during the task and failure of spatial motor learning. The results further suggest
that T-817MA is useful for treatment of neurodegenerative disorders of dopaminergic neurons
exhibiting psychiatric symptoms and/or cognitive dysfunctions.
Disclosures: T. Kimura, None; A.H. Tran, None; H. Nishijo, None; T. Ono, None.
Poster
247. Parkinson's Disease Interventions: Animal and Clinical Models
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 247.18/T1
Topic: C.02.d. Therapies
Support: NIH Grant K08NS060948
American Parkinson Disease Association Cotzias Memorial Fellowship
Title: Differential neuroprotective effects of 14-3-3 proteins in PD models
Authors: *T. A. YACOUBIAN 1 , S. R. SLONE 1 , S. HAMAMICHI 2 , A. J. HARRINGTON 2 , K.
A. CALDWELL 2 , G. A. CALDWELL 2 , D. G. STANDAERT 1 ;
1 Dept Neurol, Univ. Alabama Birmingham, Birmingham, AL; 2 Dept Biol. Sci., Univ. Alabama,
Tuscaloosa, AL
Abstract: Alpha-synuclein (α-syn) plays a central role in Parkinson‟s disease, yet its mechanism
of toxicity to dopaminergic neurons is poorly understood. We have previously shown that three
14-3-3 isoforms - 14-3-3ε, γ, and ζ - are significantly downregulated in the cortex of transgenic
mice overexpression human α-syn under the PDGF promoter. These same three isoforms have
been shown to reduce α-syn aggregation in cell-based model of α-syn aggregation. Because the
14-3-3s negatively regulate apoptotic signaling pathways, we hypothesized that overexpression
of 14-3-3 proteins could be neuroprotective in PD. To address this question, we used the
dopaminergic cell line SK-N-BE(2)-M17 to create seven stable cell lines that overexpress each
of the 14-3-3 isoforms, and tested each line for their resistance to the neurotoxins rotenone and
MPP+. Cells were treated with rotenone at concentrations ranging from 0.04 to 25 κM for 48
hours, and cell death was assessed by LDH release. For the MPP+ experiments, cells were
treated with 2 to 10 mM MPP+ for 24 hours. We found that those cell lines overexpressing either
14-3-3ε, γ, or ζ were resistant to toxicity in response to both toxins. Cell death in response to
1κM rotenone in the 14-3-3ζ was reduced to 45% of that in control stable lines transfected with
the empty vector. Similarly, rotenone-induced cell death was reduced to 65% and to 55% of
control levels in the 14-3-3ε and 14-3-3γ lines, respectively. MPP+-induced death (5mM) was