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: Masaki Kobayashi, Jihoon Kim, Natsuki Kobayashi, Sungwoong Han, Chikashi Nakamura, Kazunori Ikebukuro, Koji Sode
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 349 Issue 3 Pg. 1139-44 (Oct 27 2006) ISSN: 0006-291X [Print] United States
• PMID: 16962995 (Publication Type: Journal Article)

Chemical References

• Amyloid
• alpha-Synuclein
• PQQ Cofactor

Topics

• Amyloid (metabolism)
• Microscopy, Atomic Force
• Molecular Structure
• PQQ Cofactor (chemistry, pharmacology)
• Protein Binding
• Spectrum Analysis
• alpha-Synuclein (metabolism, ultrastructure)