University of Texas System

Gelin Wang

Steven L McKnight

Joseph Ready

Andrew A Pieper

Ting Han

Xiaodong Wang

Patrick G Harran

Provided herein are methods for identifying a compound having cell-protective (e.g., neuroprotective) activity. Compounds identified therefrom are also provided. These compounds can be used to treat various diseases, disorders, or conditions associated with, for example, unwanted cell death.

Neuroprotective chemicals and methods for identifying and using same

Ornithine &#x3b4;-aminotransferase (OAT) facilitates microtubule assembly in addition to its aminotransferase activity in mitochondria. An N-terminal proteolysis of the first 17 amino acids of OAT block its transport to the mitochondria. The resultant truncated protein (OATC) forms specific complexes with mitotic spindle promoting proteins such as Eg5 and takes on a Ran-dependent spindle-assembly activity. Methods and compositions for inhibiting mitotic spindle assembly in a cell by specifically inhibiting OAT, and methods for screening for inhibitors of (1) the spindle-assembly function of OAT, (2) the protease that N-truncates OAT, (3) the OAT/RanGTP association and (4) the OAT/Eg5 association are disclosed.

Ornithine aminotransferase (OAT): a target for anticancer drugs

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Plano, TX, United States of America

Gelin Wang