Neuronal Dopamine Transporter Associated Proteins (DTRAP)

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Katherine L. Widnell, M.D., Ph.D.
Johns Hopkins, Maryland

Abstract

The dopamine transporter (DAT) is found in the substantia nigra and striatum, brain areas involved in classic PD as well as toxin-induced parkinsonism. We know that DAT permits toxins such as MPTP and 6-OHDA to enter dopaminergic neurons. But what regulates DAT, and could DAT be the entry site for other as yet unidentified endogenous or exogenous toxins that destroy dopamine neurons? Dr. Katherine Windell (Johns Hopkins University School of Medicine) hopes to identify proteins that interact with and modulate DAT (dopamine transporter associated proteins or DTRAPs) in order to better understand how DAT regulates uptake of dopamine and neurotoxins such as MPTP in healthy and PD brains. DTRAPs could prove useful as markers for susceptibility for PD and as potential targets for therapeutic interventions.

Progress Report (as of 3/2003)

Dr. Katherine L. Widnell and her Johns Hopkins (Baltimore) colleagues have used their funds in various attempts to ascertain the functions of the dopamine transporter (DAT), a protein that is known to play a role in the reuptake of exogenous (via drug dosage) dopamine in the synapses or spaces between nerve endings in the brain. Using cloned yeast cells that they themselves sequenced, they have worked to learn if specific gene mutations or polymorphisms are associated with toxin-induced parkinsonism, possibly with human Parkinson’s disease. The connection would be through a possible interaction between a genetic and/or environmental susceptibility to PD.

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