The concealed side of caspases: beyond a killer of cells

Abstract

Since the late 20th century, researchers have known that caspases are a pillar of cell death, particularly apoptosis. However, recent advances in cell biology have unraveled the multiple roles of caspases. These enzymes have an unconventional role in cell proliferation, differentiation, and invasion. As a result, caspase deregulation can fuel the fire of cancer, incite flames of inflammation, flare neurodegenerative disorders, and exacerbate skin pathologies. Several therapeutic approaches toward caspase inhibition have been investigated, but can caspase inhibitors harness the maladaptive effect of these proteases without causing significant side effects? A few studies have exploited caspase induction for cancer or adoptive cell therapies. Here, we provide a compelling picture of caspases, starting with their evolution, their polytomous roles beyond cell death, the flaws of their deregulation, and the merits of targeting them for therapeutic implications. Furthermore, we provide a deeper understanding of the evolution of caspase-related research up to the current era, pinpointing the role of caspases in cell survival and aiding in the development of effective caspase-targeted therapies.

Keywords: Cancer; Caspase; Cell death; Differentiation; Inflammation; Neurodegenerative disease; Proliferation; Survival.

Fig. 1

The role of caspases in programmed cell death

Fig. 2

Caspases induced proliferation

Fig. 3

Caspase activation via complex assembly

Fig. 4

Caspase deregulation and disease

Fig. 5

Therapeutic implications of caspase inhibitors