Tetracycline derivatives resist the assembly behavior of human islet amyloid polypeptide.

Tetracycline derivatives resist the assembly behavior of human islet amyloid polypeptide. Biochimie. 2020 Apr 21;: Authors: Xu J, Zhao C, Huang X, Du W Abstract The misfolding of amyloid proteins is closely correlated with the pathogenesis of protein conformation-related diseases, such as Alzheimer's disease (AD), prion disease, and type 2 diabetes mellitus (T2DM). The deposition of human islet amyloid polypeptide (hIAPP) and amyloid-β (Aβ) protein is entangled in AD and diabetes mellitus. The development of potential inhibitors is a feasible therapeutic strategy to treat these diseases by resisting peptide aggregation. Doxycycline is a typical clinical antibiotic that has been utilized in neurodegenerative studies. However, the roles of tetracyclines in hIAPP aggregation remain unclear. Herein, we studied the inhibitory effects of three tetracycline derivatives, namely, minocycline hydrochloride (1), methacycline hydrochloride (2), and doxycycline (3), on the fibril formation and cytotoxicity of hIAPP and compared with that of Aβ. The well-known 3 was selected and compared with 1 and 2. Tetracycline derivatives acted as effective inhibitors to reverse the self-assembly of hIAPP and Aβ, and disaggregate the aged peptides fibrils into mostly monomers. Tetracycline derivatives also reduced the cytotoxicity induced by amyloid peptide oligomerization. Further molecular mechanism studies revealed hydrophobic and hydrogen bond interact...
Source: Biochimie - Category: Biochemistry Authors: Tags: Biochimie Source Type: research