A newly discovered neurotoxin ADTIQ associated with hyperglycemia and Parkinson's disease

Biochemical and Biophysical Research Communications
Bing-Jie XieYulin Deng

Abstract

Diabetes is associated with an increased risk of Parkinson's disease (PD). Number of studies have suggested that methylglyoxal (MGO) induced by diabetes is related to PD. However, very little is known about its molecular mechanism. On other hand, 1-acetyl-6, 7- dihydroxyl-1, 2, 3, 4- Tetrahydroisoquinoline(ADTIQ) is a dopamine (DA)-derived tetrahydroisoquinoline (TIQ), a novel endogenous neurotoxins, which was first discovered in frozen Parkinson's disease human brain tissue. While ADTIQ precursor methylglyoxal was also found in diabetic patients related to the glucose metabolism and diabetic patients. LC-MS/MS, 1H NMR and infrared spectroscopy identified the structure of ADTIQ. The Annexin V-FITC/PI, MTT and western blot analysis were used to measure the neurotoxicity of ADTIQ. The levels of ADTIQ and methylglyoxal were detected by LC-MS/MS. Here we report the chemical synthesis of ADTIQ, demonstrate its biosynthesis in SH-SY5Y neuroblastoma cell line and investigate its role in the pathogenesis of PD. In addition, a significant increase in the level of ADTIQ was detected in the brains of transgenic mice expressing mutant forms (A53T or A30P) of α-synuclein. ADTIQ also reduced the cell viability and induced mitochondrial apopt...Continue Reading

References

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Citations

Apr 20, 2016·Free Radical Biology & Medicine·Raquel Requejo-Aguilar, Juan P Bolaños
Jul 20, 2019·Journal of Huntington's Disease·Inês Caldeira BrásTiago Fleming Outeiro
Mar 8, 2016·Movement Disorders : Official Journal of the Movement Disorder Society·Hugo Vicente MirandaTiago Fleming Outeiro
Sep 17, 2016·Medicinal Research Reviews·Paulo MatafomeRaquel Seiça
Dec 25, 2019·Parkinson's Disease·Fauze Camargo MalufAlzira Alves de Siqueira Carvalho
Jun 23, 2018·Frontiers in Neuroscience·Paula A Q Videira, Margarida Castro-Caldas

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