6 research outputs found
In silico and In vivo Evaluation of Oxidative Stress Inhibitors Against Parkinson's Disease using the C. elegans Model
Background: Parkinson's disease ranks second, after Alzheimer's as the major neurodegenerative disorder, for which no cure or disease-modifying therapies exist. Ample evidence indicate that PD manifests as a result of impaired anti-oxidative machinery leading to neuronal death wherein Cullin-3 has ascended as a potential therapeutic target for diseases involving damaged anti-oxidative machinery. Objective: The design of target specific inhibitors for the Cullin-3 protein might be a promising strategy to increase the Nrf2 levels and to decrease the possibility of ``off-target'' toxic properties. Methods: In the present study, an integrated computational and wet lab approach was adopted to identify small molecule inhibitors for Cullin-3. The rational drug designing process comprised homology modeling and derivation of the pharmacophore for Cullin-3, virtual screening of Zinc natural compound database, molecular docking and Molecular dynamics based screening of ligand molecules. In vivo validations of an identified lead compound were conducted in the PD model of C. elegans. Results and Discussion: Chu center dot strategy yielded a potential inhibitor; (Glide score = -12.31), which was evaluated for its neuroprotective efficacy in the PD model of C. elegans. The inhibitor was able to efficiently defend against neuronal death in PD model of C. elegans and the neuroprotective effects were attributed to its anti-oxidant activities, supported by the increase in superoxide dismutase, catalase and the diminution of acetylcholinesterase and reactive oxygen species levels. In addition, the Cullin-3 inhibitor significantly restored the behavioral deficits in the transgenic C. elegans. Conclusion: Taken together, these findings highlight the potential utility of Cullin-3 inhibition to block the persistent neuronal death in PD. Further studies focusing on Cullin-3 and its mechanism of action would be interesting
Comparative Glycomics of Fat Globule Membrane Glycoconjugates from Buffalo (<i>Bubalus bubalis</i>) Milk and Colostrum
The health-promoting effects of milk
fat globule membrane (MFGM)
glycoconjugates has attracted curiosity especially with regard to
the challenges encountered to unravel the glycan complexities of MFGM
glycoproteins and glycosphingolipids. In this context, we characterized
glycans present in buffalo milk and colostrum fat globule membranes
by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF)
MS analysis by adopting chemoselective glycoblotting technique. Unlike
human and bovine MFGM glycoproteins, the variations were obvious with
respect to their number, size, heterogeneity, and abundance among
the samples analyzed. Among N-linked glycans, mono-, di-, and trisialyl
glycans were apparent in colostrum, while MFGM predominantly
contained mono- and disialyl glycans, in addition to neutral and high-mannose
glycoforms. The structural assignments of major glycans were confirmed
by TOF/TOF analysis. Core 1 O-glycans were more common in both samples,
and the major glycosphingolipids were GM3 and GD3 irrespective of
the samples analyzed. The colostrum N-glycans, being effective antibacterials
against human pathogens, established the structure–function
relationship of oligosaccharides in early milk in providing innate
protection to the newborn