Melatonin binds with high affinity and specificity to beta‐amyloid: LC‐MS provides insight into Alzheimer's disease treatment. Issue 10 (1st September 2021)

• Record Type: Journal Article
• Authors: Dai, Yaqian; Peng, Liduo; Liu, Yajing; Xu, Yuanhong; Qiao, Jinping
• Is Part Of: FEBS open bio. Volume 11:Issue 10(2021)
• Page Start: 2800
• Page End: 2806
• Publication Date: 2021-09-01
• Subjects: Alzheimer's disease -- beta‐amyloid -- melatonin -- receptor binding assay -- liquid chromatography–mass spectrometry; Molecular biology -- Periodicals; Cytology -- Periodicals; Life sciences -- Periodicals; Biological Science Disciplines -- Periodicals; Molecular Biology -- Periodicals; Cell Biology -- Periodicals; Cytology; Life sciences; Molecular biology; Periodicals; 572.805
• DOI: 10.1002/2211-5463.13279
• Languages: English
• ISSNs: 2211-5463

Abstract

Abstract : To study the potential relationship between melatonin and beta‐amyloid (Abeta), we established a liquid chromatography–mass spectrometry (LC‐MS) method to quantitatively analyze melatonin, deuterated isotopes (melatonin‐D4), and internal standard 6‐iodo‐2‐(4'‐dimethylamino‐) phenyl‐imidazo(1, 2) pyridine (IMPY) under positive (+) mode. The gradient elution was set to 6 min, and the corresponding peak time of melatonin and its isotope melatonin‐D4 was 3.14 min, while the peak time for the internal standard IMPY was 3.24 min. Next, we established and optimized the molecule receptor saturation binding assay based on LC‐MS to determine the melatonin affinity for beta‐amyloid (Abeta). Melatonin showed a high and specific binding for Abeta. The corresponding equilibrium dissociation constant ( K d) of melatonin with Abeta 1‐40 and Abeta 1‐42 was 814.37 ± 36.62 and 628.33 ± 13.57 nmol·L −1 ; besides, the K d of melatonin with mixed plaques (1‐40 and 1‐42) was 461.13 ± 45.37 nmol·L −1 . The results may suggest the potential mechanism of action of MT on Abeta and provide a theoretical basis for the improvement of MT treatment of Alzheimer's disease. Abstract : Our study is the first to show the direct binding of melatonin with beta‐amyloid, suggests the potential mechanism of action of MT on beta‐amyloid, and provides a theoretical basis for the improvement of MT treatment of AD.