The present invention relates to novel .alpha.-keto carbonyl calpain inhibitors for the treatment of neurodegenerative diseases and neuromuscular diseases including Duchenne Muscular Dystrophy, Becker Muscular Dystrophy and other muscular dystrophies. Disuse atrophy and general muscle wasting can also be treated. Diseases of the eye, in particular cataract, can be treated as well. Generally all condition where elevated levels of calpains are involved can be treated. The compounds of the invention may also inhibit other thiol proteases such as cathepsin B, cathepsin H, cathepsin L, papain or the like. Multicatalytic Protease also known as proteasome may also be inhibited and the compounds can therefore be used to treat cell proliferative diseases such as cancer, psoriasis, and restenosis. The compounds of the present invention are also inhibitors of cell damage by oxidative stress through free radicals can be used to treat mitochondrial disorders and neurodegenerative diseases, where elevated levels of oxidative stress are involved. In addition they introduce the expression of utrophin, which is beneficial for the treatment of Duchenne Muscular Dystrophy and Becker Muscular Dystrophy.