Apoptosis, classically initiated by caspase pathway activation, plays a prominent role during normal brain development as well as in neurodegeneration. The noncanonical, nonlethal arm of the caspase pathway is evolutionarily conserved and has also been implicated in both processes, yet is relatively understudied. Dysregulated pathway activation during critical periods of neurodevelopment due to environmental neurotoxins or exposure to compounds such as anesthetics can have detrimental consequences for brain maturation and long-term effects on behavior. In this review, we discuss key molecular characteristics and roles of the noncanonical caspase pathway and how its dysregulation may adversely affect brain development. We highlight both genetic and environmental factors that regulate apoptotic and sublethal caspase responses and discuss potential interventions that target the noncanonical caspase pathway for developmental brain injuries.

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Sarić, Hashimoto-Torii, Jevtović-Todorović, & Ishibashi.
Trends in Neurosciences April 2022