Compositions and methods for treating neural pathologies are provided. In particular, compositions and methods for treating neural pathologies including axonal degeneration are provided. The compositions include peptide .alpha.-ketomides optionally in combination with a second therapeutic agent. Another aspect of the invention provides compositions and methods for treating hyperproliferative disorders. Exemplary compositions for treating hyperproliferative disorders include an anti-proliferative agent such as paclitaxel, in combination with a calpain inhibitor such as AK295.