SAGE-Hindawi Access to Research Parkinson’s Disease Volume 2010, Article ID 650794, 16 pages doi:10.4061/2010/650794 Research Article Effects of Various Flavonoids on the α-Synuclein Fibrillation Process Xiaoyun Meng, 1 Larissa A. Munishkina, 1 Anthony L. Fink, 1 and Vladimir N. Uversky 1, 2, 3 1 Department of Chemistry, University of California, Santa Cruz, CA 95064, USA 2 Center for Computational Biology and Bioinformatics, Department of Biochemistry and Molecular Biology, Institute for Intrinsically Disordered Protein Research, Indiana University School of Medicine, 410 W. 10th Street, HS 5009, Indianapolis, IN 46202, USA 3 Institute for Biological Instrumentation, Russian Academy of Sciences, Pushchino, Moscow 142290, Russia Correspondence should be addressed to Vladimir N. Uversky, uversky@hydrogen.ucsc.edu Received 26 May 2009; Revised 8 September 2009; Accepted 23 October 2009 Academic Editor: Mark Robert Cookson Copyright © 2010 Xiaoyun Meng et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. α-Synuclein aggregation and fibrillation are closely associated with the formation of Lewy bodies in neurons and are implicated in the causative pathogenesis of Parkinson’s disease and other synucleinopathies. Currently, there is no approved therapeutic agent directed toward preventing the protein aggregation, which has been recently shown to have a key role in the cytotoxic nature of amyloidogenic proteins. Flavonoids, known as plant pigments, belong to a broad family of polyphenolic compounds. Over 4,000 flavonoids have been identified from various plants and foodstuffs derived from plants and have been demonstrated as potential neuroprotective agents. In this study 48 flavonoids belonging to several classes with structures differing in the position of double bonds and ring substituents were tested for their ability to inhibit the fibrillation of α-synuclein in vitro. A variety of flavonoids inhibited α-synuclein fibrillation, and most of the strong inhibitory flavonoids were also found to disaggregate preformed fibrils. 1. Introduction Parkinson’s disease (PD) is a chronic progressive disease, characterized clinically by resting tremor, bradykinesia (slowness in initiating movements), and rigidity. As only a small number of cases are diagnosed before the age of 50, PD is typically considered an aging disease, with a prevalence of approximately 2% after the age of 65 [1]. The cause of this neurodegenerative disease is still mysterious, although considerable evidence suggests a multifactorial etiology involving genetic susceptibility and environmental factors. In PD, neuronal death is localized to dopaminergic neurons in the substantia nigra region of the brain stem and precedes appearance of symptoms. It is believed that ca. 70% of neurons may have died by the time symptoms become apparent [2]. Diagnosis can only be definitively confirmed post mortem, by histopathological examination for the pigmented neuron loss and the presence of Lewy bodies (LBs) and Lewy neuritis (LNs) [3]. LBs are spherical protein inclusions found in the cytoplasm of surviving nigral neurons consisting of a dense core surrounded by a halo of radiating fibrils of α-synuclein, the major component of LBs [4]. A variety of other proteins have also been identified in LBs [5, 6]. However, both the mechanism underlying the formation of LBs and their pathogenic relevance are still unclear [7, 8]. Substantial evidence suggests that the aggregation of α- synuclein is a critical step in the etiology of PD [9–11]. The following observations are among the most compelling for the involvement of α-synuclein and its aggregation in PD: (i) fibrils of α-synuclein are observed in LBs and LNs, the characteristic hallmarks of the PD pathology [4, 12, 13]; (ii) three missense mutations, A53T, A30P, and E46K in α- synuclein, lead to familial early onset Parkinson’s disease [14–16]; A53T and A30P were known to increase the aggre- gation propensity of α-synuclein [17, 18]; (iii) genetic studies have shown that several cases of familial early onset PD are caused by overexpression of α-synuclein due to duplication or triplication of the α-synuclein gene locus (SNCA)[19, 20].