Institute for Molecular Bioscience (IMB) Centre for Inflammation and Disease Research, University of Queensland, St Lucia, QLD, Australia.
Institute for Molecular Bioscience (IMB) Centre for Inflammation and Disease Research, University of Queensland, St Lucia, QLD, Australia.
Trends Immunol. 2022 Nov;43(11):877-885. doi: 10.1016/j.it.2022.09.010. Epub 2022 Oct 11.
Activated microglia foster a neurotoxic, inflammatory environment in the mammalian central nervous system (CNS) that drives the pathology of neurodegenerative diseases including Parkinson's disease (PD). Moreover, mitochondrial fission promotes microglial inflammatory responses in vitro. Given that the NLRP3 inflammasome and mitochondria are central regulators of both inflammation and PD, we explore potential functions for the NLRP3 inflammasome and mitochondrial dynamics in PD. Specifically, we propose that inducible microglial mitochondrial fission can promote NLRP3-dependent neuroinflammation in hereditary and idiopathic PD. Further in-depth exploration of this topic can prompt valuable discoveries of the underlying molecular mechanisms of PD neuroinflammation, identify novel candidate anti-inflammatory therapeutics for PD, and ideally provide better outcomes for PD patients.
激活的小胶质细胞在哺乳动物中枢神经系统 (CNS) 中营造出一种神经毒性、炎症性环境,从而推动包括帕金森病 (PD) 在内的神经退行性疾病的病理发生。此外,线粒体裂变促进体外小胶质细胞的炎症反应。鉴于 NLRP3 炎性体和线粒体是炎症和 PD 的核心调节剂,我们探讨了 NLRP3 炎性体和线粒体动力学在 PD 中的潜在功能。具体而言,我们提出诱导性小胶质细胞线粒体裂变可促进遗传性和特发性 PD 中 NLRP3 依赖性神经炎症。进一步深入探讨这一课题可以促使人们对 PD 神经炎症的潜在分子机制有更深入的了解,为 PD 确定新的候选抗炎治疗药物,并为 PD 患者提供更好的治疗效果。