title: Pyrroloquinoline quinone (PQQ) prevents fibril formation of alpha-synuclein.
abstract: Pyrroloquinoline quinone (PQQ) is a noncovalently bound cofactor in the bacterial oxidative metabolism of alcohols. PQQ also exists in plants and animals. Due to its inherent chemical feature, namely its free-radical scavenging properties, PQQ has been drawing attention from both the nutritional and the pharmacological viewpoint. alpha-Synuclein, a causative factor of Parkinson's disease (PD), has the propensity to oligomerize and form fibrils, and this tendency may play a crucial role in its toxicity. We show that PQQ prevents the amyloid fibril formation and aggregation of alpha-synuclein in vitro in a PQQ-concentration-dependent manner. Moreover, PQQ forms a conjugate with alpha-synuclein, and this PQQ-conjugated alpha-synuclein is also able to prevent alpha-synuclein amyloid fibril formation. This is the first study to demonstrate the characteristics of PQQ as an anti-amyloid fibril-forming reagent. Agents that prevent the formation of amyloid fibrils might allow a novel therapeutic approach to PD. Therefore, together with further pharmacological approaches, PQQ is a candidate for future anti-PD reagent compounds.
authors.affiliation: Department of Biotechnology, Graduate School of Engineering, Tokyo University of Agriculture and Technology, 184-8588 Tokyo, Koganei, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Jihoon
authors.initials: J
authors.lastname: Kim
authors.forename: Natsuki
authors.initials: N
authors.lastname: Kobayashi
authors.forename: Sungwoong
authors.initials: S
authors.lastname: Han
authors.forename: Chikashi
authors.initials: C
authors.lastname: Nakamura
authors.forename: Kazunori
authors.initials: K
authors.lastname: Ikebukuro
authors.forename: Koji
authors.initials: K
authors.lastname: Sode
mesh_terms: D000682:Amyloid / Q000378:metabolism; D018625:Microscopy, Atomic Force; D015394:Molecular Structure; D045542:PQQ Cofactor / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding; D013057:Spectrum Analysis; D051844:alpha-Synuclein / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D000682:Amyloid; D051844:alpha-Synuclein; D045542:PQQ Cofactor