Synaptic dysfunction

Altered synaptic activity and cognitive deficits are associated with multiple neurodegenerative diseases. Metalloproteases are implicated in several molecular pathways that regulate synaptic biology, and deregulated metalloprotease activity is associated with diseases of cognition such as AD. GDE2 loss affects synapse numbers through the deregulation of RECK (a potent metalloprotease inhibitor), and mice lacking GDE2 exhibit a range of cognitive deficits [Nakamura et al., Daudelin et al.]. Current studies are examining the consequences of GDE2 loss on synaptic function and investigating how GDE2 regulation of RECK regulates metalloprotease-dependent mechanisms involved in synaptic activity.

Methodologies used in these studies include biochemistry, cell and molecular biology, mouse genetics, proteomics, primary cultures, viral work, cellular and animal models of neurodegeneration, electrophysiology, and imaging.