Occurrence and distribution of salsolinol-like compound, 1-acetyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (ADTIQ) in Parkinsonian brains

Abstract

Parkinson's disease (PD) arises from the loss of dopaminergic neurons in the substantia nigra. 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) is well known to cause Parkinsonism in humans with neurotoxicity specific for dopaminergic neurons. The experience with MPTP supports the hypothesis that endogenous or xenobiotic neurotoxins are involved in the pathogenesis of PD in humans. In our study, 1-acetyl-6, 7-dihydroxy-1, 2, 3, 4-tetrahydro-isoquinoline (ADTIQ), a novel compound, was found in frozen human brain tissues. The formation of ADTIQ was demonstrated using dopamine and methylglyoxal under physiological conditions. Methylglyoxal is a by-product of glycolysis. ADTIQ and its precursors, dopamine and methylglyoxal, were detected in different regions of frozen human brains such as the substantia nigra, caudate nucleus, putamen, frontal cortex, and the cerebellum. A significant difference in ADTIQ levels between control and Parkinson's patients was found; for instance, the ADTIQ level in putamen of PD patients was 0.76 ± 0.27 nmol/g compared to 0.10 ± 0.01 nmol/g in control. Our results might indicate that ADTIQ is possibly related to Parkinson's disease.

Catechol Tetrahydroisoquinolines Enhance a-Synuclein Aggregation and Specify the Neurotoxicity to Dopaminergic Neurons

“…In vivo study, HPLC-ESI-MS/MS results showed that the concentration of ADTIQ was 63.6 ± 4.6 fM/mg wet tissue in the substantia nigra of rat [73]. In putamen of PD patients, the level of ADTIQ was higher than that in controls, which suggested that this novel compound might be related to PD [15]. And ADTIQ is endogenously synthesized from the condensation of dopamine and methylglyoxal (MGO).…”

“…CTIQs and their derivatives can be synthesized based on different active aldehydic derivatives and DA product or its metabolites, such as 1-methyl-6,7-dihydroxyl-1,2,3,4-tetrahydroisoquinoline(Sasolinol,Sal),1-acetyl-6,7-dihydroxyl-1,2,3,4-tetrahydroisoqu-inoline (ADTIQ) and 6,7-dihydroxyl-1,2,3,4-tetrahydro-isoquinoline (norsalsolinol,norsal) [12,15,16]. These CTIQs listed above could be reacted into N-methylnorsalsolinol (NM-NorSal), N-methylsalsolinol (NM-Sal) and N-methyl-ADTIQ (NM-ADTIQ) by nitrogen methyltransferase respectively, and then generated to ion [17].…”

On the Relationship between Energy Metabolism, Proteostasis, Aging and Parkinson’s Disease: Possible Causative Role of Methylglyoxal and Alleviative Potential of Carnosine

“…Not only can MG directly damage mitochondria [65,66] and may be associated with age-related cognitive decline [67], but the bicarbonyl can also react with dopamine [68,69] to form 1-acetyl-6,7-dihydroxy-1,2,3,4-tetrahydro-isoquinaline (ADTIQ), which is a salsolinol-like compound [69]. ADTIQ not only accumulates in PD brains but also mimics the effects of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) whose effects on mitochondria resemble the changes associated with PD [69].…”

“…ADTIQ not only accumulates in PD brains but also mimics the effects of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) whose effects on mitochondria resemble the changes associated with PD [69]. Further evidence supporting the proposed link between MG, dopamine and generation of the neurotoxin ADTIQ is shown by the increased levels of glycolytic enzymes, MG and ADTIQ in the brains of diabetic rats [70].…”

Common defects of mitochondria and iron in neurodegeneration and diabetes (MIND): A paradigm worth exploring

“…A recent investigation found that methylglyoxal mediated modification of the Na v 1.8 sodium channel is associated with hyperalgesia in diabetic neuropathy [173], implicating a direct role for methylglyoxal in diabetes-induced nociceptive pain. In addition, a novel neurotoxin known as ADTIQ (1-acetyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline) discovered in the brains of PD patients has been found to be the result of methylglyoxal reacting with dopamine [174]. It has been suggested that this neurotoxin, the result of altered bioenergetic homeostasis and a specific neurotransmitter, might be a common pathogen between Parkinson’s disease and diabetes.…”