Druggability of mortalin for cancer and neuro-degenerative disorders.

Mortalin is a member of Hsp70 family of stress chaperones. It was first identified as a protein involved in the senescence of mouse cells. Genetic studies revealed that there are two mouse mortalin alleles coding for two proteins (mot-1 and mot-2) that differ in only two amino acids in the carboxy-terminus, but have contrasting activities. Whereas mot-1 accelerated senescence, mot-2 extended the lifespan of mouse cells in culture. In human cells, only one kind of mortalin protein has been identified so far and is shown to be functionally equivalent to mouse mot-2. Whereas mortalin is enriched in cancer cells and contributes to carcinogenesis, the old age brain disorders show its deficiency. As we demystify its deux de machina, accumulating evidence reveal that mortalin may be "druggable" bidirectionally to either treat cancer or neuro-degenerative disorders.