Maneb, a widely-used dithiocarbamate fungicide, remains in the environment and exerts adverse health effects. Epidemiological evidence shows that maneb exposure is associated with a higher risk of Parkinson’s disease (PD), one of the most common neurodegenerative diseases. However, the molecular mechanisms underlying maneb-induced neurotoxicity remain unclear. Here we investigated the toxic effects and the underlying mechanisms of maneb on the degeneration of dopaminergic cells and α-synuclein in A53T transgenic mice. In SH-SY5Y cells, exposure to maneb reduces cell viability, triggers neuronal apoptosis, induces mitochondrial dysfunction, and generates reactive oxidative species (ROS) in a dose-dependent manner. Furthermore, Western blot analysis found that the mitochondrial apoptosis pathway (Bcl-2, Bax, cytochrome c, activated caspase-3) and the PKA/CREB signaling pathway (PKA, PDE10A, CREB, p-CREB) were changed by maneb both in vitro and in vivo. In addition, the activation of the mitochondrial apoptosis pathway induced by maneb was attenuated by activating PKA. Therefore, these results suggest that the PKA/CREB signaling pathway is involved in maneb-induced apoptosis. This study provides novel insights into maneb-induced neurotoxicity and the underlying mechanisms, which may serve as a guide for further toxicological assessment and standard application of maneb.

Maneb 是一种广泛使用的二硫代氨基甲酸酯类杀菌剂，会残留在环境中并对健康产生不利影响。流行病学证据表明，接触代森锰会增加患帕金森病 (PD) 的风险，帕金森病是最常见的神经退行性疾病之一。然而，代森锰引起的神经毒性的分子机制仍不清楚。在这里，我们研究了代森锰对 A53T 转基因小鼠多巴胺能细胞和 α-突触核蛋白退化的毒性作用和潜在机制。在 SH-SY5Y 细胞中，暴露于代森锰会降低细胞活力，触发神经细胞凋亡，诱导线粒体功能障碍，并以剂量​​依赖的方式产生活性氧化物质 (ROS)。此外，Western blot分析发现线粒体凋亡途径（Bcl-2、Bax、细胞色素c, 激活的 caspase-3) 和 PKA/CREB ​​信号通路 (PKA, PDE10A, CREB, p-CREB)在体外和体内都被代森锰改变。此外，代森锰诱导的线粒体凋亡途径的激活通过激活 PKA 减弱。因此，这些结果表明 PKA/CREB ​​信号通路参与代森锰诱导的细胞凋亡。该研究为代森锰引起的神经毒性及其潜在机制提供了新的见解，可作为进一步毒理学评估和代森锰标准应用的指南。