Exploring the role of parthanatos in CNS injury: Molecular insights and therapeutic approaches

Background: Central nervous system (CNS) injury causes severe organ damage due to both damage resulting from the injury and subsequent cell death. However, there are currently no effective treatments for countering the irreversible loss of cell function. Parthanatos is a poly (ADP-ribose) polymerase 1 (PARP-1)dependent form of programmed cell death that is partly responsible for neural cell death. Consequently, the mechanism by which parthanatos promotes CNS injury has attracted significant scientific interest. Aim of review: Our review aims to summarize the potential role of parthanatos in CNS injury and its molecular and pathophysiological mechanisms. Understanding the role of parthanatos and related molecules in CNS injury is crucial for developing effective treatment strategies and identifying important directions for future in-depth research. Key scientific concepts of review: Parthanatos (from Thanatos, the personification of death according to Greek mythology) is a type of programmed cell death that is initiated by the overactivation of PARP-1. This process triggers a cascade of reactions, including the accumulation of poly(ADP-ribose) (PAR), the nuclear transloca- tion of apoptosis-inducing factor (AIF) after its release from mitochondria, and subsequent massive DNA frag- mentation caused by migration inhibitory factor (MIF) forming a complex with AIF. Secondary molecular mechanisms, such as excitotoxicity and oxidative stress-induced overactivation of PARP-1, significantly exacerbate neuronal damage following initial mechanical injury to the CNS. Furthermore, parthanatos is not only associated with neuronal damage butalso interacts withvarious other types ofcell death. This review focuses onthe latest research concerning the parthanatos cell death pathway, particularly consideringits reg- ulatory mechanisms and functions in CNS damage. We highlight the associations between parthanatos and different cell types involved in CNS damage and discuss potential therapeutic agents targeting the parthana- tos pathway. (c) 2023 The Authors. Published by Elsevier B.V. on behalf of Cairo University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).