α-Crystallin chaperone mimetic drugs inhibit lens γ-crystallin aggregation: Potential role for cataract prevention

Islam, Sidra; Michael, T.; Frank, Brett S.; Hom, Grant L; Wheeler, Samuel; Fujioka, Hisashi; Wang, Benlian; Minocha, Geeta; Sell, David R.; Fan, Xingjun; Lampi, Kirsten J.; Monnier, Vincent M.

doi:10.1016/j.jbc.2022.102417

Cited by 7 publications

(4 citation statements)

References 84 publications

(116 reference statements)

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“…These and other technological advances can support and lead to new therapeutic approaches e.g. (417,418) to protect image formation and improve the quality of life for the elderly. A lens is much more than an optical element in the visual system.…”

Section: Discussionmentioning

confidence: 99%

Insights into the biochemical and biophysical mechanisms mediating the longevity of the transparent optics of the eye lens

Quinlan

Clark

2022

Journal of Biological Chemistry

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Section: Discussionmentioning

confidence: 99%

Insights into the biochemical and biophysical mechanisms mediating the longevity of the transparent optics of the eye lens

Quinlan

Clark

2022

Journal of Biological Chemistry

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“…In the past several decades, researchers have been dedicated to achieve this goal. These include, for example, Islam et al screened small molecules that might protect gama-Crystallin from destabilization and aggregation after H 2 O 2 exposure, which provided insights for the existence of drugs and small molecules maintaining the transparency of lens [22]. Huang Y. et al found Biliverdin/Bilirubin redox pair could mitigate oxidative damage of LECs via NF-kB/iNOS and Nrf2/HO-1 pathways [23].…”

Section: Discussionmentioning

confidence: 99%

Identification of tRNA-derived small RNAs expression profiles and their potential functions in age-related cataract

Liu

Zhang

Jiang

et al. 2023

Preprint

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Object: To identify the expression profiles and demonstrate the potential functions of tRNA-derived small RNAs (tsRNAs) in the formation of age-related cataract (ARC). Methods: Human lens epithelial cell line (HLE-B3 cells) were treated with H2O2, small RNA sequencing analysis was performed to identify expression profiles of tsRNAs in control and H2O2-treated HLE-B3 cells. Then, GO and KEGG enrichment analysis were employed to illustrate the potential functions of differentially expressed (DE) tsRNAs and target genes in ARC. Finally, quantitative real-time PCR assay was used to verify the expression patterns of DE tsRNAs. Results: Totally 604 DE tsRNAs (329 upregulated and 275 downregulated) were obtained between control and H2O2-treated HLE-B3 cells. Bioinformatic analysis results showed that calcium signaling pathway may mainly participate in the formation of ARC. Conclusion: Our results indicated that tsRNAs may be associated with the pathogenesis of ARC, and thus might be potential diagnostic and therapeutic targets for ARC.

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“…Myo-inositol, a sugar alcohol found in healthy lens, is found to be an efficient suppressor of the aggregation of γD-Crystallin. , Ortho-vanillin, found in the essential oils of some plants, acts as an effective inhibitor of its aggregation on exposure to UV–C light . The screening of 2560 Federal Drug Agency-approved drugs by Monnier et al suggested that two of them, closantel and gambogic acid, were able to inhibit the heating-induced aggregation of bovine γ-crystallins …”

Section: Introductionmentioning

confidence: 99%

“…25 The screening of 2560 Federal Drug Agency-approved drugs by Monnier et al suggested that two of them, closantel and gambogic acid, were able to inhibit the heating-induced aggregation of bovine γ-crystallins. 26 One group of such potential drugs could be polyphenols. Polyphenols are natural occurring compounds that are known to have an antioxidant effect.…”

Section: ■ Introductionmentioning

confidence: 99%

Quercetin-Loaded Nanocarriers as Effective Inhibitors for Copper Metal Ion-Induced γD-Crystallin Aggregation

Goswami,

Das,

Deep

2024

Langmuir

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Cataract is one of the leading causes of blindness worldwide. Till date, the only solution for cataracts is surgery, which is a resource-intensive solution. A much simpler solution is to find a potential drug that could inhibit aggregation. It is well established that nonamyloid aggregates of eye lens protein result in cataract. γD-Crystallin, a thermodynamically stable protein, is one of the most abundant proteins in the core of the eye lens and is found to aggregate under stress conditions, leading to the cataract. It has also been found that in cataractous lens, the concentration of metals like copper is elevated significantly as compared to healthy eye lens, suggesting their role in inducing aggregation. In our present study, aggregation of γD-Crystallin was carried out in the presence of Cu (II). Using techniques like turbidity assay, CD spectroscopy, ANS binding assay, and microscopic studies like TEM, it could be confirmed that protein aggregates in the presence of Cu (II) and the nature of aggregates is amorphous. Various polyphenols were tested to suppress aggregation of the protein. Quercetin was observed to be the most efficient. To overcome the problems associated with the delivery of polyphenols, such as solubility and bioavailability, quercetin was encapsulated in two types of nanocarriers. Their characterization was done using TEM, DLS, and other techniques. The potency of quercetin-loaded CS-TPP/ CS-PLGA NPs as inhibitors of γD-Crystallin aggregation was confirmed by various experiments.

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α-Crystallin chaperone mimetic drugs inhibit lens γ-crystallin aggregation: Potential role for cataract prevention

Cited by 7 publications

References 84 publications

Insights into the biochemical and biophysical mechanisms mediating the longevity of the transparent optics of the eye lens

Insights into the biochemical and biophysical mechanisms mediating the longevity of the transparent optics of the eye lens

Identification of tRNA-derived small RNAs expression profiles and their potential functions in age-related cataract

Quercetin-Loaded Nanocarriers as Effective Inhibitors for Copper Metal Ion-Induced γD-Crystallin Aggregation

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