The overall goal of this laboratory is to understand mechanisms underlying neuronal death in several neurodegenerative disorders. Our work has shown that such inhibition causes an activation of specific glutamate receptors on susceptible neurons which is followed by excitotoxic cell death associated with sequelae such as sodium and calcium ion influxes and potentiation of oxidative stress, i.e., production of toxic reactive oxygen species. We are currently probing the mechanisms underlying the initiation of receptor activation, including membrane changes and second messenger involvement.
Cell death occurs by both necrotic and apoptotic pathways.
In all these conditions, mitochondrial dysfunction has been suggested. Such studies, combined with genetic studies, are necessary for future rational therapy for these diseases. Energy stress-induced dopamine loss in glutathione peroxidase over expressing transgenic mice and in glutathione depleted mesencephalic cultures. Attenuation of excitotoxic cell swelling and Gaba release by the GABA transport inhibitor, SKF 89976A. Mol. Relative vulnerability of dopamine and GABA neurons in mesencephalic culture to inhibition of succinate dehydrogenase by malonate and3-nitropropionate and protection by NMDA receptor blockade.