Elucidation of the cause of Caribbean parkinsonism and prevention in other area

在法属西印度群岛的瓜德鲁普，非典型帕金森症或进行性核上性麻痹的发病率很高，所有被调查的患者都服用了草药茶或番荔枝科的热带水果。当地居民食用水果，也喝叶子制成的茶。在本研究中，我们使用液相色谱-串联质谱（LC/MS/MS）与多反应监测（MRM）检测低分子量的神经毒性苄基异喹啉衍生物在番荔枝科。我们检测到牛心果碱和N-甲基coculaurine在每个番荔枝样品检查，除了果肉和种子。在番荔枝果实中未检出。在所有样品中均未检出去甲牛心果碱。这三种化合物对SH-SY 5 Y神经母细胞瘤细胞具有毒性，并抑制线粒体呼吸复合物I。这是可能的苄基异喹啉衍生物牛心果碱和N-甲基coculaurine的摄取和它们在大脑中的积累可能与当地地方病的发病机制。

In Guaderoupe, the French West Indies, there is a high incidence of atypical parkinsonism or progressive supranuclear palsy, and all of the investigated patients had taken herbal tea or tropical fruits of the Annonaceae family. Local inhabitants consume the fruits, and also drink tea made from the leaves. In the present study, we used liquid chromatography-tandem mass spectrometry (LC/MS/MS) with multiple reaction monitoring (MRM) to detect low-molecular-weight neurotoxic benzylisoquinoline derivatives in the Annonaceae family. We detected reticuline and N-methylcoculaurine in every Annona muricata sample examined, except for pulp and seed. They were not detected in sweetsop fruits. Norreticuline was not detected in any sample. These three compounds were toxic to SH-SY5Y neuroblastoma cells and inhibited mitochondrial respiratory complex I. It is possible that uptake of the benzylisoquinoline derivatives reticuline and N-methylcoculaurine and their accumulation in the brain may be related to the pathogenesis of the local endemic disease.