Abstract:
:α-Synuclein aggregation is centrally implicated in Parkinson's disease (PD). It involves multi-step nucleated polymerization process via the formation of dimers, soluble toxic oligomers and insoluble fibrils. In the present study, we synthesized a novel compound viz., Curcumin-glucoside (Curc-gluc), a modified form of curcumin and studied its anti-aggregating potential with α-synuclein. Under aggregating conditions in vitro, Curc-gluc prevents oligomer formation as well as inhibits fibril formation indicating favorable stoichiometry for inhibition. The binding efficacies of Curc-gluc to both α-synuclein monomeric and oligomeric forms were characterized by micro-calorimetry. It was observed that titration of Curc-gluc with α-synuclein monomer yielded very low heat values with low binding while, in case of oligomers, Curc-gluc showed significant binding. Addition of Curc-gluc inhibited aggregation in a dosedependent manner and enhanced α-synuclein solubility, which propose that Curc-gluc solubilizes the oligomeric form by disintegrating preformed fibrils and this is a novel observation. Overall, the data suggest that Curc-gluc binds to α-synuclein oligomeric form and prevents further fibrillization of α-synuclein; this might aid the development of disease modifying agents in preventing or treating PD.
journal_name
Curr Pharm Desjournal_title
Current pharmaceutical designauthors
Gadad BS,Subramanya PK,Pullabhatla S,Shantharam IS,Rao KSdoi
10.2174/138161212798919093subject
Has Abstractpub_date
2012-01-01 00:00:00pages
76-84issue
1eissn
1381-6128issn
1873-4286pii
BSP/CPD/E-Pub/000804journal_volume
18pub_type
杂志文章abstract:: ...
journal_title:Current pharmaceutical design
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journal_title:Current pharmaceutical design
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journal_title:Current pharmaceutical design
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journal_title:Current pharmaceutical design
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abstract::DNA methylation, a major regulator of epigenetic modifications has been shown to alter the expression of genes that are involved in aspects of glucose metabolism such as glucose intolerance, insulin resistance, β-cell dysfunction and other conditions, and it ultimately leads to the pathogenesis of type 2 diabetes mell...
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abstract::A large body of evidence has accumulated indicating involvement of oxidative stress (OS) in the mode of action of various bioactive substances, including those of the immune system. The data for anticancer drugs (main and miscellaneous) are summarized herein. Although diverse origins pertain, reactive oxygen species (...
journal_title:Current pharmaceutical design
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更新日期:2000-02-01 00:00:00
abstract::Inhibition of carbonic anhydrase (CA, EC 4.2.1.1) isoforms present in the eyes (CA I, II, IV and XII), with sulfonamides such as acetazolamide, methazolamide, ethoxzolamide and dichlorophenamide, is still widely used for the systemic treatment of glaucoma. The mechanism of action of these drugs consists in inhibition ...
journal_title:Current pharmaceutical design
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更新日期:2008-01-01 00:00:00
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更新日期:2010-01-01 00:00:00
abstract::The production of autoreactive antibodies from self-reactive B cells results in the formation of immune complexes that deposit in tissue and fix complement, contributing to the pathogenesis of rheumatoid arthritis (RA). Earlier mouse models emphasize the importance of autoreactive antibodies formed against "self" prot...
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journal_title:Current pharmaceutical design
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更新日期:2020-01-01 00:00:00
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journal_title:Current pharmaceutical design
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更新日期:2013-01-01 00:00:00
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journal_title:Current pharmaceutical design
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