Abstract Details

Title Development of Nurr1-RXR Heterodimer Biased Agonists for Parkinson's Disease

Topic Movement Disorders

Presentation(s) P02 - (-)

Poster/Presentation
Number 077

Objective

Background BACKGROUND: Nurr1 is a nuclear hormone receptor (NucHR) strongly implicated in the growth, maintenance, and survival of dopaminergic neurons. Nurr1 is poorly accessed by small molecule drugs, but forms heterodimers with other NucHRs that are.

Design/Methods DESIGN/METHODS: BRET2 assays were performed with R. Luciferase and GFP tagged receptors as described (Tan et al., 2007). Compounds with suitable profiles were tested for neuroprotective properties in primary midbrain cultures damaged by MPP+ or in 6-hydroxydopamine lesioned rats.

Results RESULTS: Compounds that preferentially activated Nurr1-RXR heterodimers over RXR-RXR homodimers were identified. One compound was tested and found to restore tyrosine hydroxylase (TH) phenotype and neurite outgrowth in MPP+ treated primary cultures of midbrain dopamine neurons and to rescue dopamine neurons and reverse motor and non-motor behavioral deficits in rats previously lesioned with 6-hydroxydopamine.

Conclusions CONCLUSIONS: Such compounds may offer promise as therapies for altering the progression of Parkinson's disease.

Authors/Disclosures
PRESENTER	No disclosure on file
	No disclosure on file
David R. Hubbard, MD	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Ludwig Kappos, MD, FAAN (RC2NB, University Hospital Basel)	Dr. Kappos has nothing to disclose.

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