Pyrroloquinoline quinone (PQQ) prevents fibril formation of alpha-synuclein.
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.
Kobayashi
Masaki
M
Department of Biotechnology, Graduate School of Engineering, Tokyo University of Agriculture and Technology, 184-8588 Tokyo, Koganei, Japan.
Kim
Jihoon
J
Kobayashi
Natsuki
N
Han
Sungwoong
S
Nakamura
Chikashi
C
Ikebukuro
Kazunori
K
Sode
Koji
K
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
D000682:Amyloid; D051844:alpha-Synuclein; D045542:PQQ Cofactor