Weissbach, Herbert

Biological homeostasis relies on protective mechanisms that respond to cellular oxidation
caused primarily by free radical reactions. Methionine sulfoxide reductases Msr are a class of
enzymes that reverse oxidative damage to methionine. The focus of this study is on the
relationship between Msr and dopamine in Drosophila. Dopaminergic neurons in drosophila
have comparable roles to those found in humans. A deficit in dopamine leads to the onset of
many neurological disorders including the loss of fine motor control—a neurodegenerative
condition characteristic of Parkinson’s disease PD. We have found that dopamine levels in the
heads of MsrAΔ/ΔBΔ/Δ mutants are significantly reduced in comparison
to the wild type. In addition, we have found that TH protein and expression levels are markedly
reduced in an Msr-deficient system. Our findings suggest that it is possible the Msr system plays
an important role in maintaining dopaminergic neurons alive, and thus, is protectant of the CNS.

Biological homeostasis relies on protective mechanisms that respond to cellular oxidation caused primarily by free radical reactions. Methionine sulfoxide reductases (Msr) are a class of enzymes that reverse oxidative damage to methionine in proteins. The focus of this study is on the relationship between Msr and dopamine levels in Drosophila. Dopaminergic neurons in Drosophila have comparable roles to those found in humans. A deficit in dopamine leads to the onset of many neurological disorders including the loss of fine motor control—a neurodegenerative condition characteristic of Parkinson’s disease (PD). We found that dopamine levels in the heads of MsrAΔ/ΔBΔ/Δ mutants are significantly reduced in comparison to MsrA ⁺/⁺ B⁺/⁺ heads. In addition, wefound protein and expression levels are markedly reduced in an Msr-deficient system. Our findings suggest an important role for the Msr system in the CNS.