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Small molecules are being explored intensively for their applications as therapeutic molecules in the management of metabolic and neurological disorders. The natural small molecules can inhibit protein aggregation and underlying cellular pathogenesis of neurodegenerative diseases involving multi‐factorial mechanisms of action. Certain natural small molecular inhibitors of pathogenic protein aggregation are highly efficient and have shown promising therapeutic potential. In the present study, Shikonin (SHK), a natural plant‐based naphthoquinone has been investigated for its aggregation inhibition activity against α‐synuclein (α‐syn) and the neuroprotective potential in Caenorhabditis elegans (C. elegans). SHK significantly inhibited aggregation of α‐syn at sub‐stochiometric concentrations, delayed the linear lag phase and growth kinetics of seeded and unseeded α‐syn aggregation. The binding of SHK to the C‐terminus of α‐syn maintained α‐helical and disordered secondary structures with reduced beta‐sheet content and complexity of aggregates. Further, in C. elegans transgenic PD models, SHK significantly reduced α‐syn aggregation, improved locomotor activity and prevented dopaminergic (DA) neuronal degeneration, indicating the neuroprotective role of SHK. The present study highlights the potential of natural small molecules in the prevention of protein aggregation that may further be explored for their therapeutic efficacy in the management of protein aggregation and neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

The accumulation of protein aggregates as intracellular inclusions interferes with cellular protein homeostasis leading to protein aggregation diseases. Protein aggregation results in the formation of several protein conformers including oligomers and fibrils, where each conformer has its own structural characteristic and proteotoxic potential. The present study explores the effect of alpha-synuclein (α-syn) conformers on the activity and spontaneous refolding of firefly luciferase. Of the different conformers, α-syn monomers delayed the inactivation of luciferase under thermal stress conditions and enhanced the spontaneous refolding of luciferase. In contrast, the α-syn oligomers and fibrils adversely affected luciferase activity and refolding, where the oligomers inhibited spontaneous refolding, whereas a pronounced effect on the inactivation of native luciferase was observed in the case of fibrils. These results indicate that the oligomers and fibrils of α-syn interfere with the refolding of luciferase and promote its misfolding and aggregation. The study reveals the differential propensities of various conformers of a pathologically relevant protein in causing inactivation, structural modifications and misfolding of other proteins, consequently resulting in altered protein homeostasis. [ABSTRACT FROM AUTHOR]

It is a broad concept which encompasses a wide range of drug delivery systems through the skin/mucosa using any forces such as Lorentz, shock waves, pressure by gas, or electrophoresis. The system drives the drug through the skin/mucosa virtually nullifying the use of hypodermic needle. They are available in reusable forms. This technology can be highly useful in pediatric patients as it helps avoid anxiety, fear, and phobia like emotions. It can be further classified based on their working, type of load, mechanism of drug delivery, and site of delivery. [ABSTRACT FROM AUTHOR]