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Natasha Wadlington |
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DJ-1 is one of several genes known to contribute to
Parkinson’s disease (PD). DJ-1 is thought to cause PD by its loss of
function, however that function is unknown. In PD patient’s
brains, oxidative damage to lipids, proteins, and DNA has been
observed. Under oxidative conditions, stabilized Nrf2 translocates
into the nucleus and activates antioxidant response element (ARE) genes. These ARE
genes prevent increased damage of cellular organelles and molecules from
oxidative stress. Recently a study by Clements et al.
2006 showed that knocking down DJ-1 decreased Nrf2 protein and ARE
gene levels. It can be hypothesized that DJ-1 loss of function decreases the
stability and subsequently activity of Nrf2 thus decreasing the antioxidant
response and contributing to oxidative damage. My thesis project will revolve
around elucidating the mechanisms of how DJ-1 aids in either the stability
and/or translocation of Nrf2 and whether the oxidative state of DJ-1 has any
effect on Nrf2. |
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11/05/08 |
