Investigation of Parkinson's disease causing substances

1，2，3，4-四氢异喹啉(TIQ)类化合物存在于哺乳动物体内，其化学结构类似于MPTP，已被认为是内源性帕金森病致病化合物的候选化合物。最近有报道称，1-苄基-1，2，3，4-四氢异喹啉(1BnTIQ)存在于人脑脊液和小鼠脑中，并提出1BnTIQ是由2-苯乙胺和苯乙醛生物合成的，苯乙醛是由B型一氧化氮合酶生成的2-苯乙胺的代谢产物。PD患者脑脊液中的1BnTIQ含量高于其他神经系统疾病患者。此外，反复服用这种化合物会导致猴子和小鼠患上帕金森症。1BnTIQ可通过多巴胺转运体(DAT)抑制HEK293细胞对多巴胺的摄取，提示1BnTIQ通过DAT以1-甲基-4-苯基吡啶离子的形式被摄取，1-甲基-4-苯基吡啶是多巴胺能神经毒素MPTP的活性代谢产物。我们还报道了包括1BnTIQ在内的各种四氢异喹啉衍生物抑制线粒体呼吸和电子传递复合体的作用。

1, 2, 3, 4-Tetrahydroisoqpinoline (TIQ) derivatives, which chemically resemble MPTP, exist in mammals and have been proposed as candidates for endogenous parkinsonogenic compounds.It was recently reported 1-benzyl-1, 2, 3, 4-tetrahydroisoqpinoline (1BnTIQ) is present in human cerebrospinal fluid and mouse brain, and proposed that 1BnTIQ is biosynthesized from 2-phenylethylamine and phenylacetaldehyde which is a metabolite of 2-pherrylethylamine generated by monoanrine oxidase-type B. The 1BnTIQ content in cerebrospinal fluid of patients with PD is higher than that of patients with other neurological diseases. Further, repeated administration of this compound induced parkinsonism in the monkey and mouse. 1BnTIQ inhibited dopamine uptake through dopamine transporter (DAT) expressed in HEK293 cells, suggesting that 1BnTIQ is uptaken through DAT as 1-methyl-4-phenylpyridinium ion, which is an active metabolite of dopaminergic neurotoxin, MPTP. We also reported that various tetrahydroisoquinoline derivatives including 1BnTIQ inhibited mitochondrial respiration and the electron transfer complexes.