Esterification of PQQ Enhances Blood-Brain Barrier Permeability and Inhibitory Activity against Amyloidogenic Protein Fibril Formation

• DOI: 10.1021/acschemneuro.8b00355
• Publication Date: 2018-08-03T20:19:41Z
• Authors: Kaori Tsukakoshi; Wataru Yoshida; Masaki Kobayashi; Natsuki Kobayashi; Jihoon Kim; Toshisuke Kaku; Toshitsugu Iguchi; Kazuo Nagasawa; Ryutaro Asano; Kazunori Ikebukuro; Koji Sode
• Keywords: Neurons; 0301 basic medicine; Amyloid; Amyloid beta-Peptides; Esterification; Cell Survival; PQQ Cofactor; Amyloidogenic Proteins; Esters; Protein Aggregation, Pathological; Peptide Fragments; Permeability; Prion Proteins; Mice; 03 medical and health sciences; Blood-Brain Barrier; Cell Line, Tumor; alpha-Synuclein; Animals; Humans

Several neurodegenerative diseases have a common pathophysiology where selective damage to neurons results from the accumulation of amyloid oligomer proteins formed via fibrilization. Considering that formation oligomers leads cytotoxicity, development chemical compounds are able effectively cross blood-brain barrier (BBB) and inhibit this conversion and/or fibrils is essential for disease therapy. We previously reported pyrroloquinoline quinone (PQQ) prevented aggregation fibrillation α-synuclein, β1–42 (Aβ1–42), mouse prion protein. To develop novel drug against based on PQQ, it necessary improve insufficient BBB permeability PQQ. Here, we show an esterified compound PQQ-trimethylester (PQQ-TME), has twice than PQQ in vitro. Moreover, PQQ-TME exhibited greater inhibitory activity Aβ1–42, These indicated esterification could be useful approach developing PQQ-based inhibitor.