Pyridoxamine and Aminoguanidine Attenuate the Abnormal Aggregation of β-Tubulin and Suppression of Neurite Outgrowth by Glyceraldehyde-Derived Toxic Advanced Glycation End-Products

• Main Authors: Hayahide Ooi (Author), Ryuto Nasu (Author), Ayako Furukawa (Author), Masayoshi Takeuchi (Author), Yoshiki Koriyama (Author)
• Format: Book
• Published: Frontiers Media S.A., 2022-06-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

Diabetes mellitus (DM) has been identified as a risk factor for the onset and progression of Alzheimer's disease (AD). In our previous study, we demonstrated that glyceraldehyde (GA)-derived toxic advanced glycation end-products (toxic AGEs, TAGE) induced similar alterations to those observed in AD. GA induced dysfunctional neurite outgrowth via TAGE-β-tubulin aggregation, which resulted in the TAGE-dependent abnormal aggregation of β-tubulin and tau phosphorylation in human neuroblastoma SH-SY5Y cells. However, the effects of inhibitors of AGE formation on dysfunctional neurite outgrowth caused by GA-induced abnormalities in the aggregation of β-tubulin and tau phosphorylation remain unknown. Aminoguanidine (AG), an AGE inhibitor, and pyridoxamine (PM), a natural form of vitamin B6 (VB6), are effective AGE inhibitors. Therefore, the present study investigated whether AG or PM ameliorate TAGE-β-tubulin aggregation and the suppression of neurite outgrowth by GA. The results obtained showed that AG and PM inhibited the formation of TAGE-β-tubulin, mitigated the GA-induced suppression of neurite outgrowth, and reduced GA-mediated increases in tau phosphorylation levels. Collectively, these results suggest the potential of AG and PM to prevent the DM-associated onset and progression of AD.

Item Description

1663-9812
10.3389/fphar.2022.921611