single-molecule metallo-neurobiology

Single-molecule Metallo-neurobiology

Abnormal metal homeostasis within/between neurons impacts the onset and progression of neurodegenerative disorders like Alzheimer’s disease, yet detailed mechanisms are largely unknown. Our group studies the dynamics and mechanisms of protein machineries involved in copper trafficking within/between neurons using single-molecule techniques. We aim to understand how metals affect neuronal signaling and cause neurodegenerative diseases.

Research Directions

Break down of neuronal metal homeostasis can occur through irregular metal trafficking either within neurons or at synapses. Our two research directions are (1) metal trafficking in neurons and (2) metal trafficking at the synapse.

Simplified scheme for Cu homeostasis in neurons and synapses.

Atox1 and CCS traffic Cu to ATP7A and SOD1 through protein-protein interaction. ATP7A and synaptic vesicles are responsible for Cu release into the synaptic cleft. Synaptic Cu then interacts with α-syn and APP for signaling between presynaptic and postsynaptic neurons.