A matter of regeneration and repair: caspases as the key molecules

Researchers have been focused on understanding the pathogenesis of human diseases. They have been working to find the roles of caspases in the balance between apoptosis, autophagy, pyroptosis, and necroptosis, and also in the regeneration of damaged tissue. At this point, besides their death-inducing roles, new findings indicate the role of caspases in proliferation for maintaining the viability of cells in response to signals from apoptotic cells. Recently, determining cell fate has also been identified among other functions of caspases. Findings indicate that caspases direct cellular pathways to cell differentiation by suppressing stem cell self-renewal. The common opinion about the related mechanism is that low and transient caspase activation leads to terminal differentiation by affecting the expression of key genes related to differentiation. Moreover, caspases are essential proteases in the regulation and modulation of the repair process. In repair, they have roles in apoptosis, release of inflammatory cytokines and chemokines, promotion of cell migration, and immune cell infiltration. However, paracrine signaling through caspase activation leads to cell proliferation after cancer therapy and causes tumor relapse, which complicates the current therapy. In this scope, we have reviewed the main mechanisms of pathological, regenerative, and restorative effects of caspases.