Oxidative stress and inflammation are established factors associated with neurodegenerative diseases, including two common alpha-synucleinopathies: Parkinson's disease (PD) and Dementia with Lewy Bodies (DLB). The pathological hallmark of PD and DLB are cytoplasmic aggregates called Lewy bodies containing the neuronal protein alpha synuclein. Sporadic factors, which account for >90% of disease cases, have been shown to increase levels of reactive oxygen species (ROS) that are implicated in alpha synuclein aggregation/ pathogenesis. The goal of this research is to determine whether ROS-oxidized metabolites can accelerate alpha synuclein aggregation in vitro. The biological relevance of the in vitro results will be addressed by evaluating the effect of oxidative metabolites on cells expressing alpha synuclein, and by quantifying the levels of ROS-oxidized metabolites in diseased brain tissue. These experiments will address a possible role for ROS-oxidized metabolites in sporadic alpha-synucleinopathies.
| Gao, Jianmin; Bosco, Daryl A; Powers, Evan T et al. (2009) Localized thermodynamic coupling between hydrogen bonding and microenvironment polarity substantially stabilizes proteins. Nat Struct Mol Biol 16:684-90 |
