Ginsenoside Rb1 inhibits fibrillation and toxicity of alpha-synuclein and disaggregates preformed fibrils.

Autor: Ardah MT; Department of Biochemistry, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates., Paleologou KE; Department of Molecular Biology and Genetics, Democritus University of Thrace, Alexandroupolis, Greece., Lv G; Department of Biochemistry, Weill Cornell Medical College, New York, NY, USA., Menon SA; Department of Biochemistry, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates., Abul Khair SB; Department of Biochemistry, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates., Lu JH; State Key Lab of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, China., Safieh-Garabedian B; Department of Biological and Environmental Sciences, Qatar University, Doha, Qatar., Al-Hayani AA; Department of Anatomy, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia., Eliezer D; Department of Biochemistry, Weill Cornell Medical College, New York, NY, USA., Li M; School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong., El-Agnaf OM; 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.
Jazyk: angličtina
Zdroj: Neurobiology of disease [Neurobiol Dis] 2015 Feb; Vol. 74, pp. 89-101. Date of Electronic Publication: 2014 Nov 15.
DOI: 10.1016/j.nbd.2014.11.007
Abstrakt: 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.
(Copyright © 2014 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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