Effect of (R)-Salsolinol and N-Methyl-(R)-Salsolinol on the Balance Impairment Between Dopamine and Acetylcholine in Rat Brain: Involvement in Pathogenesis of Parkinson Disease

Zhu, Wei; Wang, Dan; Zheng, Jiajia; An, Yarui; Wang, Qingjiang; Zhang, Wen; Jin, Litong; Gao, Hongying; Lin, Longnian

doi:10.1373/clinchem.2007.097725

Cited by 35 publications

(24 citation statements)

References 32 publications

(28 reference statements)

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“…This result is different from earlier research, which showed that only (R)-Sal could be detected in human brain with PD . However, it is similar to the report where the enantiomeric ratio of (R)-/(S )-Sal was approximately 2 (Zhu et al 2008). The disagreements in above mentioned findings may be because salsolinol synthase in our research was extracted from the rat brain and the activity of the enzyme in rat brain is lower than the activity in human brain with PD.…”

Section: Discussionsupporting

confidence: 85%

“…Figure 1 illustrates two proposed synthetic pathways of Sal from dopamine and acetaldehyde (AcH). The first one produces the racemic mixture of both enantiomers (Robbins et al 1968;Zhu et al 2008), the latter produces (R)-Sal only Rojkovicova et al 2008). Accordingly, the surplus of (R)-Sal detected in the human brain may be biosynthesized by this putative enzyme.…”

Section: Introductionmentioning

confidence: 99%

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Enzymatic condensation of dopamine and acetaldehyde: a salsolinol synthase from rat brain

et al. 2011

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Salsolinol (1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline; Sal) is structurally similar to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, which is supposed to have a role in the development of Parkinson-like syndrome in both human and non-human subjects. In the human brain, the amount of (R)-enantiomer of Sal is much higher than (S )-enantiomer, suggesting that a putative enzyme may participate in the synthesis of (R)-salsolinol, called (R)-salsolinol synthase. In this study, the (R)-salsolinol synthase activity in the condensation of dopamine and acetaldehyde was investigated in the crude extracts from the brains of Sprague Dawley rats. Identification of the enzymatic reaction products and enzyme activity detection were achieved by HPLC-electrochemical detection. The discovery of this enzyme activity in rat's brain indicates the natural existence of (R)-salsolinol synthase in the brains of humans and rats, and it is distributed in most brain regions of rat with higher activity in soluble proteins extracted from striatum and substantia nigra.

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Section: Discussionsupporting

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Enzymatic condensation of dopamine and acetaldehyde: a salsolinol synthase from rat brain

et al. 2011

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“…Salsolinol is demonstrated to be formed from DA and acetaldehyde by an (R)-salsolinol synthase-mediated condensation, N-methylated into (R)-N-methylsalsolinol by a neutral (R)-salsolinol N-methyltransferase, and then oxidized into an ion of 6,7-dihydroxy-1,2-dimethyl-isoqiolinium, an analogue of 1-methyl-4-phenylpyridinium (MPP + ). The toxicity of N-methylsalsolinol and its oxidation product for dopaminergic neurons has previously been examined in vivo and in vitro (8,9).…”

Section: Introductionmentioning

confidence: 99%

Formation of a salsolinol-like compound, the neurotoxin, 1-acetyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, in a cellular model of hyperglycemia and a rat model of diabetes

Song

Xin

Xie

et al. 2013

International Journal of Molecular Medicine

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Abstract. There are statistical data indicating that diabetes is a risk factor for Parkinson's disease (PD). Methylglyoxal (MG), a biologically reactive byproduct of glucose metabolism, the levels of which have been shown to be increase in diabetes, reacts with dopamine to form 1-acetyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (ADTIQ); this formation may provide further insight into the connection between PD and diabetes. In this study, we investigated the role of ADTIQ in these two diseases to determine in an aim to enhance our understanding of the link between PD and diabetes. To this end, a cell model of hyperglycemia and a rat model of diabetes were established. In the cell model of hyperglycemia, compared with the control group, the elevated glucose levels promoted free hydroxyl radical formation (p<0.01). An ADTIQ assay was successfully developed and ADTIQ levels were detected and quantified. The levels of its precursors, MG and dopamine (DA), were determined in both the cell model of hyperglycemia and the rat model of diabetes. The proteins related to glucose metabolism were also assayed. Compared with the control group, ADTIQ and MG levels were significantly elevated not only in the cell model of hyperglycemia, but also in the brains of rats with diabetes (p<0.01). Seven key enzymes from the glycolytic pathway were found to be significantly more abundant in the brains of rats with diabetes. Moreover, it was found that adenosine triphosphate (ATP) synthase and superoxide dismutase (SOD) expression levels were markedly decreased in the rats with diabetes compared with the control group. Therefore, ADTIQ expression levels were found to be elevated under hyperglycemic conditions. The results reported herein demonstrate that ADTIQ, which is derived from MG, the levels of which areincreased in diabetes, may serve as a neurotoxin to dopaminergic neurons, eventually leading to PD. IntroductionDiabetes mellitus (DM), as a state of chronic hyperglycemia, and Parkinson's disease (PD) are diseases which consist a global health threat. In recent years, there have been increasing data indicating that hyperglycemia is associated with an increased risk of developing PD (1,2). However, the mechanisms underlying the association between hyperglycemia and PD have not yet been elucidated.Deng and Rajput (6) were the first to report, in 2001, that 1-acetyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (ADTIQ), a salsolinol-like compound, is found at highly concentrated levels in the brains of patients who suffer from PD (3). When the brains of deceased patients with PD were compared to those of normal subjects, it was found that patients with PD presented elevated levels of ADTIQ in all the examined brain areas. This finding indicated that elevated ADTIQ expression levels may be one of the mechanisms involved in the increased risk patients with diabetes have of developing PD (4).Formation of a salsolinol-like compound, the neurotoxin, 1-acetyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, in a cellular model of hyperglycem...

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“…Sal is known to be synthesized from DA and acetaldehyde (AcH) and has two enantiomers, (S)-Sal and (R)-Sal. (R)-Sal is dominant, which can be further catalyzed to N-methyl-(R)-salsolinol (NM(R)Sal) by N-methyltransferase and then oxidize into 1,2-dimethyl-6,7-dihydroxyisoquinolinium ion (DMDHIQ+) [39]. Sal can be detected in various regions of human brain, but it is highly concentrated in the striatum and substantia nigra [40,41].…”

Section: The Major Neurotoxic Ctiqsmentioning

confidence: 99%

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

Chen¹,

Lu²,

Duan³

et al. 2017

J Alzheimers Dis Parkinsonism

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Effect of (R)-Salsolinol and N-Methyl-(R)-Salsolinol on the Balance Impairment Between Dopamine and Acetylcholine in Rat Brain: Involvement in Pathogenesis of Parkinson Disease

Cited by 35 publications

References 32 publications

Enzymatic condensation of dopamine and acetaldehyde: a salsolinol synthase from rat brain

Enzymatic condensation of dopamine and acetaldehyde: a salsolinol synthase from rat brain

Formation of a salsolinol-like compound, the neurotoxin, 1-acetyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, in a cellular model of hyperglycemia and a rat model of diabetes

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

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