title: Ginsenoside Rb1 inhibits fibrillation and toxicity of alpha-synuclein and disaggregates preformed fibrils.
abstract: Compelling evidence indicates that α-synuclein (α-syn) aggregation plays a central role in the pathogenesis of Parkinson's disease (PD) and other synucleinopathies. Identification of compounds that inhibit or reverse the aggregation process may thus represent a viable therapeutic strategy against PD and related disorders. Ginseng is a well-known medicinal plant that has been used in East Asia for more than two thousand years to treat several conditions. It is now understood that the pharmacological properties of ginseng can be attributed to its biologically active components, the ginsenosides, which in turn have been shown to have neuroprotective properties. We therefore sought to determine for the first time, the potential of the most frequently used and studied ginsenosides, namely Rg1, Rg3 and Rb1, as anti-amyloidogenic agents. The effect of Rg1, Rg3 and Rb1 on α-syn aggregation and toxicity was determined by an array of biophysical, biochemical and cell-culture-based techniques. Among the screened ginsenosides, only Rb1 was shown to be a potent inhibitor of α-syn fibrillation and toxicity. Additionally, Rb1 exhibited a strong ability to disaggregate preformed fibrils and to inhibit the seeded polymerization of α-syn. Interestingly, Rb1 was found to stabilize soluble non-toxic oligomers with no β-sheet content, that were susceptible to proteinase K digestion, and the binding of Rb1 to those oligomers may represent a potential mechanism of action. Thus, Rb1 could represent the starting point for designing new molecules that could be utilized as drugs for the treatment of PD and related disorders.
authors.affiliation: Department of Biochemistry, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.
authors.forename: Mustafa T
authors.initials: MT
authors.lastname: Ardah
authors.affiliation: Department of Molecular Biology and Genetics, Democritus University of Thrace, Alexandroupolis, Greece.
authors.forename: Katerina E
authors.initials: KE
authors.lastname: Paleologou
authors.affiliation: Department of Biochemistry, Weill Cornell Medical College, New York, NY, USA.
authors.forename: Guohua
authors.initials: G
authors.lastname: Lv
authors.affiliation: Department of Biochemistry, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.
authors.forename: Sindhu A
authors.initials: SA
authors.lastname: Menon
authors.affiliation: Department of Biochemistry, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.
authors.forename: Salema B
authors.initials: SB
authors.lastname: Abul Khair
authors.affiliation: State Key Lab of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, China.
authors.forename: Jia-Hong
authors.initials: JH
authors.lastname: Lu
authors.affiliation: Department of Biological and Environmental Sciences, Qatar University, Doha, Qatar.
authors.forename: Bared
authors.initials: B
authors.lastname: Safieh-Garabedian
authors.affiliation: Department of Anatomy, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Abdulmonem A
authors.initials: AA
authors.lastname: Al-Hayani
authors.affiliation: Department of Biochemistry, Weill Cornell Medical College, New York, NY, USA.
authors.forename: David
authors.initials: D
authors.lastname: Eliezer
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong.
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Biochemistry, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates; Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia. Electronic address: o.elagnaf@uaeu.ac.ae.
authors.forename: Omar M A
authors.initials: OM
authors.lastname: El-Agnaf
mesh_terms: D000682:Amyloid / Q000187:drug effects* / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D019286:Endopeptidase K / Q000378:metabolism; D004926:Escherichia coli; D036145:Ginsenosides / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D018696:Neuroprotective Agents / Q000494:pharmacology*; D058105:Polymerization / Q000187:drug effects; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000187:drug effects / Q000378:metabolism / Q000633:toxicity; D051844:alpha-Synuclein / Q000187:drug effects* / Q000378:metabolism / Q000633:toxicity*
chemical_list: D000682:Amyloid; D036145:Ginsenosides; D018696:Neuroprotective Agents; D011994:Recombinant Proteins; C497604:SNCA protein, human; D051844:alpha-Synuclein; C097367:ginsenoside Rg3; C442759:ginsenoside Rb1; D019286:Endopeptidase K; C035054:ginsenoside Rg1
keywords: Aggregation; Amyloid fibrils; Drug discovery; Ginsenosides; Parkinson's disease; α-Synuclein