Gelatin as a Potential Inhibitor of Insulin Amyloid Fibril Formation

Abstract

Direct inhibition of amyloid fibrillation, the primary cause of many neurodegenerative diseases, using natural and synthetic molecules is one of the therapeutic strategies to prohibit the progression of amyloid diseases. Herein, we have demonstrated that, for the first time, gelatin, a commonly used gelling agent in food, was a potent inhibitor of amyloid fibril formation using insulin, a model protein for amyloid fibrillation. Thioflavin T and turbidity data indicated concentration‐dependent inhibition of insulin amyloid fibrillation by gelatin. Atomic force microscopy envisaged the inhibition of insulin fibrillation by gelatin. The spectroscopic analysis suggested that gelatin inhibits the insulin amyloid fibrillation by stabilising the native structure of insulin. 8‐anilinonaphthalene‐1‐sulfonic acid fluorescence data indicated that gelatin prevented the accessible exposed hydrophobic regions of insulin, which is required for insulin aggregation. Studies also suggested that the anti‐amyloidogenic efficiency of a mixture containing gelatin and a known amyloid inhibitor (Ferulic acid) was higher than their individual efficiency. Since gelatin is commonly used in drug formulation, its inherent anti‐amyloidogenic character may be beneficial in the formulation of anti‐amyloidogenic compounds. Hence, the current findings may have significant implications for the development of therapeutic agents for the prevention of disease‐related amyloid proteins.

Amyloid Fibrillation of Insulin: Amelioration Strategies and Implications for Translation

“…Examples of other such natural compounds are ascorbic acid (vitamin C) and the anticancer drug paclitaxel . Additionally, gelatin has demonstrated an anti-fibrillogenic potential . These compounds not only can inhibit insulin fibrillation but also ameliorate the cytotoxicity of the fibers.…”

Molecular Aspects of Insulin Aggregation and Various Therapeutic Interventions

“…Jayamani and Shanmugam reported the use of gelatin, a common gelling agent, in the prevention of insulin aggregation . Based on spectroscopic studies and ThT assays, they proposed that gelatin stabilized the native structure of insulin.…”

Strategies for Interference of Insulin Fibrillogenesis: Challenges and Advances

“…[110] Jayamani and Shanmugam demonstrated the potential anti-amyloidogenic efficacy of gelatin against insulin amyloid formation. [111] This commonly used food gelling agent arrests insulin fibrillation by engaging the amyloid initiating hydrophobic patches of insulin and further stabilize its overall native framework. However, the antifibrillating efficacy of gelatin is further enhanced by the coexistence of ferulic acid in the mixture, as ferulic acid has high anti-amyloidogenic activity.…”