However, when the eliminated fragment is a highly reactive thioacylating agent that covalently adds to macromolecules, the parent cysteine S-conjugate is toxic. We are investigating biochemical mechanisms whereby certain cysteine S-conjugates are nephrotoxic and neurotoxic. We and others have shown that the Qn domains are especially good substrates of tissue transglutaminase.
Recent evidence suggests that the brain contains unique isoforms of tTGase.
We are in the process of characterizing brain tTGases at the biochemical and molecular level. Our eventual goal is to design selective inhibitors of these enzymes as potential therapeutic agents. J. Neurochem . A possible mechanism contributing to CAG-triplet diseases. Qn-expansion diseases with special reference to the role of tissue transglutaminase and selective vulnerability.