Investigation of Parkinson's disease causing substances

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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.