Tris (1,3-dichloro-2-propyl) phosphate (TDCPP) aggravates Parkinson’s disease neurotoxicity through ferroptosis-related oxidative stress and neuroinflammation

作者：Guangming Xie, Yulan Yang, Xinmin Zhang, Yitong Chen, Xinyuan Cao, Jun Zhang, Yanyan Jiang, Weiting Yang · 发表于：Brain Research · 年份：2025 · DOI：10.1016/j.brainres.2025.149805 · 被引用次数：5 · 研究领域：Ferroptosis and cancer prognosis、Trace Elements in Health、MicroRNA in disease regulation

Organophosphorus flame retardant TDCPP, a substitute for brominated flame retardants, is widely used in consumer products but readily leaches into the environment, posing human exposure risks. This study investigated the neurotoxic mechanisms of TDCPP in Parkinson's disease (PD). Using an MPTP-induced PD mouse model, TDCPP exposure exacerbated behavioral deficits, reduced tyrosine hydroxylase (TH)-positive neurons in the substantia nigra, and amplified neuroinflammation characterized by enhanced microglial reactivity, elevated pro-inflammatory IFN-γ, and diminished anti-inflammatory IL-4 and regulatory T cells (Tregs). Concurrently, TDCPP lowered glutathione (GSH) levels and altered ferroptosis-related protein expression, indicating oxidative stress involvement. In SH-SY5Y cells, co-treatment with TDCPP and MPTP caused mitochondrial membrane depolarization, increased reactive oxygen species (ROS), and shifted microglia into a pro-inflammatory state-evidenced by increased CD86 expression-and impaired their phagocytic clearance of α-synuclein. These findings demonstrate that TDCPP aggravates PD neurodegeneration through dual mechanisms: ferroptosis-linked oxidative stress and neuroinflammation. This study provides the first evidence linking TDCPP exposure to ferroptosis-mediated neurotoxicity in PD models, bridging environmental toxicology and neurodegenerative research. The results underscore the role of environmental pollutants in PD progression and offer critical insights fo...