Cytoskeletal abnormalities relevant to neurodegenerative disease

Changes in cytoskeletal proteins such as tau and neurofilaments are closely associated with impaired neuronal function and neurodegeneration and often involve post-translational modifications such as phosphorylation. While the kinases that carry out these modifications are increasingly known, the upstream mechanisms that initiate the signaling cascades that result in pathologic phosphorylation signatures of cytoskeletal proteins are less clear. Mice lacking GDE2 show changes in the phosphorylation of cytoskeletal proteins implicated in neurodegenerative disease [Cave et al.]. Ongoing studies are examining the mechanisms underlying this dysregulation and studying if they are altered in disease.

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