The fibrillation of α-synuclein (α-Syn) is considered a major contributor to Parkinson's disease (PD). Recent therapeutic measures have focused on inhibiting the fibrillation of α-Syn using various small molecules. We report here the effects of two different hydroxycinnamic acids; chlorogenic acid and sinapic acid on α-Syn fibrillation and have also discussed the mechanistic insights into their mode of modulation. The fluorescence spectroscopy shows that the two hydroxycinnamic acids bind with α-Syn with moderate affinity. Molecular docking studies provide a detailed insights into binding at the residue level and isothermal titration calorimetry reveals specific interactions, like hydrogen bonding, hydrophobic interactions, and van der Waals forces involved in the binding process. Fibrillation kinetics and transmission microscopic studies demonstrated that both chlorogenic acid and sinapic acid attenuate α-Syn fibrillation in a concentration dependent manner. Circular dichroism spectroscopy shows that these compounds bind with α-Syn and delay its structural transition in β-sheet containing fibrillar structures. Both the compounds are also effective even if added after the onset of fibrillation and the fibrillar species formed in the presence of these acids are unable to induce secondary nucleation in monomeric α-Syn. Such kind of structural and mechanistic insights are extremely crucial for designing therapeutic intervention in PD and other neurodegenerative diseases.
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http://dx.doi.org/10.1016/j.bbrc.2024.151195 | DOI Listing |
Biochem Biophys Res Commun
December 2024
UM-DAE Centre for Excellence in Basic Sciences, University of Mumbai, Vidhyanagri Campus, Kalina, Mumbai, 400098, India. Electronic address:
The fibrillation of α-synuclein (α-Syn) is considered a major contributor to Parkinson's disease (PD). Recent therapeutic measures have focused on inhibiting the fibrillation of α-Syn using various small molecules. We report here the effects of two different hydroxycinnamic acids; chlorogenic acid and sinapic acid on α-Syn fibrillation and have also discussed the mechanistic insights into their mode of modulation.
View Article and Find Full Text PDFInt J Biol Macromol
December 2024
Chemical Engineering Department, Stellenbosch University, Private Bag X1, Stellenbosch 7602, South Africa. Electronic address:
Cross-linkages with polysaccharides and lignin compromise hydroxycinnamic acid yields and purity in integrated biorefineries. A two-stage-alkaline-based process was sequentially optimised in a wheat straw (WS) and wheat bran (WB)-based biorefinery setup for selective co-production of hydroxycinnamic acids (p-Coumaric acid & ferulic acid) with hemicellulose at the mild-alkaline stage (MAS), and with lignin & cellulose-rich residues at severe-alkaline stage (SAS). The optimum MAS biorefining conditions gave hemicellulose, lignin, and hydroxycinnamic acid yields of 35, 60, and 85 % for WS, and 37, 72, and 66 % for WB, respectively.
View Article and Find Full Text PDFEnviron Microbiome
December 2024
Scion, Christchurch, 8011, New Zealand.
Background: Pollen is a crucial source of nutrients and energy for pollinators. It also provides a unique habitat and resource for microbiota. Previous research on the microbiome of pollen has largely focused on angiosperm systems, with limited research into coniferous gymnosperms.
View Article and Find Full Text PDFPhysiol Plant
December 2024
Plant Biotechnology Division, CSIR-Central Institute of Medicinal and Aromatic Plants (CIMAP), Lucknow, Utter Pradesh, India.
Transgenic Ocimum sanctum plants were engineered to produce vanillin by overexpressing the VpVAN gene using Agrobacterium-mediated transformation. Positive transformants developed shoots within 4-5 weeks and were transferred to a root induction medium and four independent transformants with no observed adverse effects were kept for anlysis. Quantitative RT-PCR indicated significantly higher VpVAN expression in transgenic lines AG_3 and AG_1, impacting the phenylpropanoid pathway and phenolic compound accumulation.
View Article and Find Full Text PDFInt J Mol Sci
November 2024
Department of Analytical Chemistry, Faculty of Chemistry, Adam Mickiewicz University, Uniwersytetu Poznańskiego 8, 61-614 Poznan, Poland.
This study aimed to investigate the response of L. × to the addition of selected metals in soil. Rooted cuttings were planted in pots containing soil enriched with equimolar concentrations of Pb, Zn, Al, Ni, and Cu (500 mL of 4 mM solutions of single metal salts: (Pb(NO); Zn(NO) × 6HO; Al(NO) × 9HO; Ni(NO) × 6HO; or Cu(NO) × 3HO).
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