2. Academic Validation
  3. Inhibition of amyloid formation of amyloid β (1-42), amylin and insulin by 1,5-diazacyclooctanes, a spermine-acrolein conjugate

Inhibition of amyloid formation of amyloid β (1-42), amylin and insulin by 1,5-diazacyclooctanes, a spermine-acrolein conjugate

  • Bioorg Med Chem. 2021 Sep 15;46:116391. doi: 10.1016/j.bmc.2021.116391.
Risako Kunitomi 1,  Ambara R Pradipta 2,  Haruka Kawabe 1,  Nadine Lobsiger 3,  Katsunori Tanaka 4,  Tamotsu Zako 5
Affiliations

Affiliations

  • 1 Department of Chemistry and Biology, Graduate School of Science and Engineering, Ehime University, 2-5 Bunkyo, Matsuyama, Ehime 790-8577, Japan.
  • 2 Department of Chemical Science and Engineering, School of Materials and Chemical Technology, Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro, Tokyo 152-8552, Japan; Biofunctional Synthetic Chemistry Laboratory, RIKEN Cluster for Pioneering Research, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
  • 3 Department of Chemistry and Biology, Graduate School of Science and Engineering, Ehime University, 2-5 Bunkyo, Matsuyama, Ehime 790-8577, Japan; Institute for Chemical and Bioengineering, ETH Zürich, Wolfgang-Pauli-Strasse 10, CH-8093 Zürich, Switzerland.
  • 4 Department of Chemical Science and Engineering, School of Materials and Chemical Technology, Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro, Tokyo 152-8552, Japan; Biofunctional Synthetic Chemistry Laboratory, RIKEN Cluster for Pioneering Research, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan; Biofunctional Chemistry Laboratory, Alexander Butlerov Institute of Chemistry, Kazan Federal University, 18 Kremlyovskaya Street, 420008 Kazan, Russian Federation.
  • 5 Department of Chemistry and Biology, Graduate School of Science and Engineering, Ehime University, 2-5 Bunkyo, Matsuyama, Ehime 790-8577, Japan. Electronic address: [email protected].
PMID: 34488020 DOI: 10.1016/j.bmc.2021.116391
Abstract

Amyloid aggregates of proteins are known to be involved in various diseases such as Alzheimer's disease (AD). It is therefore speculated that the inhibition of amyloid formation can play an important role in the prevention of various diseases involving amyloids. Recently, we have found that acrolein reacts with polyamines, such as spermine, and produces 1,5-diazacyclooctane, such as cyclic spermine (cSPM). cSPM could suppress the aggregation of amyloid β 1-40 (Aβ40), one of the causative proteins of AD. This result suggests the potential inhibitory effect of cSPM against Aβ 1-42 (Aβ42) and other amyloid protein aggregation which are the main pathological features of AD and Other Diseases. However, the effect on the aggregation of such proteins remains unclear. In this study, the effect of cSPM on the amyloid formation of Aβ42, amylin, and Insulin was investigated. These three amyloidogenic proteins forming amyloids under physiological conditions (pH 7.4 and 37℃) served as model and are thought to be the causative proteins of AD, type 2 diabetes, and insulin-derived amyloidosis, respectively. Our results indicate that cSPM can suppress the amyloid aggregation of these proteins and reduce cytotoxicity. This study contributes to a better understanding of means to potentially counteract diseases by the means of polyamine and acrolein.

Keywords

1,5-diazacyclooctane; Acrolein; Alzheimer's disease; Amylin; Amyloid fibrils; Amyloid-β; Insulin; Insulin-derived amyloidosis; Polyamine; Type 2 diabetes.

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