Pla2g4a, also known as phospholipase A2, group IVA (cytosolic, calcium-dependent) [2], is an enzyme that plays a crucial role in lipid metabolism, especially in the glycerophospholipid metabolism pathway [3,4]. It can catalyze the hydrolysis of glycerophospholipids, releasing fatty acids and lysophospholipids, which are involved in many biological processes such as cell membrane remodeling, inflammation, and signal transduction [2,3,4].

In cerebral ischemia-reperfusion injury, the neuronal STAT3/HIF-1α/PTRF axis upregulates Pla2g4a, leading to lipid metabolism reprogramming, mitochondrial bioenergetics alteration, and subsequent oxidative damage, which exacerbates the injury [1]. In traumatic brain injury, activation of Pla2g4a causes lysosomal membrane permeabilization (LMP), inhibits autophagy flux, and results in neurodegeneration, while its in vivo pharmacological inhibition attenuates these effects and improves neurological outcomes [2]. In platinum-resistant gastric cancer, Pla2g4a, along with ACHE, modulates the lipid profile through the glycerophospholipid metabolism pathway [3].

In conclusion, Pla2g4a is essential in lipid-related biological processes. Its dysregulation is involved in multiple disease conditions, including ischemic stroke, traumatic brain injury, and platinum-resistant gastric cancer. Research on Pla2g4a using in vivo models such as gene-targeted mouse models has provided valuable insights into the molecular mechanisms underlying these diseases, offering potential therapeutic targets [1-3].

References:

1. Jin, Weili, Zhao, Jixing, Yang, Eryan, Zhou, Junhu, Kang, Chunsheng. 2022. Neuronal STAT3/HIF-1α/PTRF axis-mediated bioenergetic disturbance exacerbates cerebral ischemia-reperfusion injury via PLA2G4A. In Theranostics, 12, 3196-3216. doi:10.7150/thno.71029. https://pubmed.ncbi.nlm.nih.gov/35547748/

2. Sarkar, Chinmoy, Jones, Jace W, Hegdekar, Nivedita, Kane, Maureen A, Lipinski, Marta M. 2019. PLA2G4A/cPLA2-mediated lysosomal membrane damage leads to inhibition of autophagy and neurodegeneration after brain trauma. In Autophagy, 16, 466-485. doi:10.1080/15548627.2019.1628538. https://pubmed.ncbi.nlm.nih.gov/31238788/

3. Chen, Menglin, Zhang, Cancan, Li, Huaizhi, Wu, Jian, Sun, Qingmin. 2024. PLA2G4A and ACHE modulate lipid profiles via glycerophospholipid metabolism in platinum-resistant gastric cancer. In Journal of translational medicine, 22, 249. doi:10.1186/s12967-024-05055-4. https://pubmed.ncbi.nlm.nih.gov/38454407/

4. Chen, Yuting, Li, Kaipeng, Zhao, Han, Gao, Mingming, Zhao, Ding. 2022. Integrated lipidomics and network pharmacology analysis to reveal the mechanisms of berberine in the treatment of hyperlipidemia. In Journal of translational medicine, 20, 412. doi:10.1186/s12967-022-03623-0. https://pubmed.ncbi.nlm.nih.gov/36076294/