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

Jiacheng Zhang; Xinli Hu; Yibo Geng; Linyi Xiang; Yuzhe Wu; Yao Li; Liangliang Yang; Kailiang Zhou

doi:10.1016/j.jare.2024.04.031

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

J Adv Res. 2024 May 3:S2090-1232(24)00174-7. doi: 10.1016/j.jare.2024.04.031. Online ahead of print.

Authors

Jiacheng Zhang¹, Xinli Hu², Yibo Geng¹, Linyi Xiang¹, Yuzhe Wu¹, Yao Li³, Liangliang Yang⁴, Kailiang Zhou⁵

Affiliations

¹ Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China; Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou 325027, China.
² Department of Orthopedics, Xuanwu Hospital of Capital Medical University, Beijing 100053, China.
³ Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China; Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou 325027, China. Electronic address: yaoli@wmu.edu.cn.
⁴ School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou 325027, China. Electronic address: liangliangyangLLL@126.com.
⁵ Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China; Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou 325027, China. Electronic address: zhoukailiang@wmu.edu.cn.

PMID: 38704090
DOI: 10.1016/j.jare.2024.04.031

Abstract

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 translocation of apoptosis-inducing factor (AIF) after its release from mitochondria, and subsequent massive DNA fragmentation 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 but also interacts with various other types of cell death. This review focuses on the latest research concerning the parthanatos cell death pathway, particularly considering its regulatory 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 parthanatos pathway.

Keywords: CNS injury; Cell death; PARP-1; Parthanatos.

Publication types

Review