Unveiling the role of iPLA2β in neurodegeneration: From molecular mechanisms to advanced therapies

• Published in: Pharmacological research Vol. 202; p. 107114
• Main Authors: Liu, Jiabin, Tan, Jieqiong, Tang, Beisha, Guo, Jifeng
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01.04.2024; Elsevier
• Subjects: IPLA2β; Lipid; Mitochondria; Neurodegeneration; PLA2G6; nSMase; AREP; FK; DMT1; CHO; iPLA2β; DP; PLA2s; PLAN; PLA2G6; CaM; iPSCs; Mitochondria; S1P; Neurodegeneration; α-Syn; TfR1; SOCE; SM; aNAD; KI; CCE; KO; BDNF; EOP; BEL; INAD; IRPs; Lipid; AR; PD; ROS; MAM; DHA
• ISSN: 1043-6618; 1096-1186
• DOI: 10.1016/j.phrs.2024.107114

Calcium-independent phospholipase A2β (iPLA2β), a member of the phospholipase A2 (PLA2s) superfamily, is encoded by the PLA2G6 gene. Mutations in the PLA2G6 gene have been identified as the primary cause of infantile neuroaxonal dystrophy (INAD) and, less commonly, as a contributor to Parkinson's disease (PD). Recent studies have revealed that iPLA2β deficiency leads to neuroinflammation, iron accumulation, mitochondrial dysfunction, lipid dysregulation, and other pathological changes, forming a complex pathogenic network. These discoveries shed light on potential mechanisms underlying PLA2G6-associated neurodegeneration (PLAN) and offer valuable insights for therapeutic development. This review provides a comprehensive analysis of the fundamental characteristics of iPLA2β, its association with neurodegeneration, the pathogenic mechanisms involved in PLAN, and potential targets for therapeutic intervention. It offers an overview of the latest advancements in this field, aiming to contribute to ongoing research endeavors and facilitate the development of effective therapies for PLAN. [Display omitted] •iPLA2β plays a crucial role in iron homeostasis, lipid metabolism, mitochondrial regulation.•Diverse functions of iPLA2β have implications for the pathogenesis of PLA2G6-associated neurodegeneration.•Recent discoveries of novel mechanisms provide potential therapeutic implications for PLA2G6-associated neurodegeneration.