REVIEW ARTICLE
The Inhibition of Amyloid Fibrillation Using the Proteolytic Products of PQQ-Modified α-Synuclein
Natsuki Kobayashi1, Jihoon Kim1, Kazunori Ikebukuro1, Koji Sode1, 2, *
Article Information
Identifiers and Pagination:
Year: 2009Volume: 3
First Page: 40
Last Page: 45
Publisher ID: TOBIOTJ-3-40
DOI: 10.2174/1874070700903010040
Article History:
Received Date: 12/12/2008Revision Received Date: 09/02/2009
Acceptance Date: 16/02/2009
Electronic publication date: 13/5/2009
Collection year: 2009
open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: (https://creativecommons.org/licenses/by/4.0/legalcode). This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
The inhibition of amyloid fibril and/or oligomer formation allows a novel therapeutic approach to neurodegenerative diseases such as Parkinson’s disease. We have previously reported that pyrroloquinoline quinone (PQQ), a cofactor in the bacterial oxidative metabolism of alcohols, prevents the amyloid formation of α-synuclein, which is the causative factor of Parkinson’s disease. Moreover, PQQ-modified α-synuclein is also able to inhibit the fibrillation of intact α- synuclein. Here, we demonstrate that PQQ-modified peptide fragments, the proteolytic products of PQQ-modified α- synuclein, prevent the amyloid formation of full-length α-synuclein, and that these inhibitory effects are derived from the PQQ modification of the peptide. Moreover, these effects are likely to be peptide-sequence-dependent. Thus, the specific interaction between the full-length α-synuclein and the peptide region of the PQQ-modified peptide prevents amyloid formation.
