The flavonoid derivative 2-(4' Benzyloxyphenyl)-3-hydroxy-chromen-4-one protects against Aß42-induced neurodegeneration in transgenic Drosophila: insights from in silico and in vivo studies.

In the pathogenesis of Alzheimer's disease (AD), it is well established that the self-association of Aß peptides into amyloid fibrils and/or plaque like aggregates causes neurotoxicity. As there is no cure for AD till date, identification of specific compounds that either inhibit the formation of Aß-fibrils or help in the dissolution of already formed amyloid plaques makes an appealing therapeutic and preventive strategy in the development of drugs. In the present study, four synthetic flavonoid derivatives (1, 2, 3 and 4) were examined for docking studies with Amyloid beta (PDB Code: 1IYT) and Amyloid fibril (PDB Code: 2BEG). Of these, compound 1 and 4 were found to be potential inhibitors, as supported by computational molecular docking studies with adequate pharmacokinetic properties. Compound 1 was further tested in vivo in transgenic AD model of Drosophila. The disease causing human Aß42 peptide was expressed in the compound eye by driving UAS-Aß42 with ey-GAL4, which caused severe degeneration in eye tissues ranging from loss of bristles, ommatidial holes to severe ommatidial disruption as revealed by digital camera imaging and scanning electron microscopy. When the Aß42 expressing larvae were grown in medium containing Compound 1, ~70 % rescue of the rough eye phenotype was observed at 75 and 100 µM concentrations. This is further corroborated by significant reduction in amyloid plaques in eye imaginal disks of compound 1 treated larvae as revealed by immuno-confocal imaging studies. Further, rescue of locomotor deficit and improved life span in compound 1 treated Aß flies also confirm the neuroprotective activity of this compound. Thus, our results support the neuroprotective efficacy of compound 1 in preventing Aß42-induced neurotoxicity in vivo and identify it as a future therapeutic agent against AD.

Development of a low cost high precision three-layer 3D artificial compound eye.

Artificial compound eyes are typically designed on planar substrates due to the limits of current imaging devices and available manufacturing processes. In this study, a high precision, low cost, three-layer 3D artificial compound eye consisting of a 3D microlens array, a freeform lens array, and a field lens array was constructed to mimic an apposition compound eye on a curved substrate. The freeform microlens array was manufactured on a curved substrate to alter incident light beams and steer their respective images onto a flat image plane. The optical design was performed using ZEMAX. The optical simulation shows that the artificial compound eye can form multiple images with aberrations below 11 µm; adequate for many imaging applications. Both the freeform lens array and the field lens array were manufactured using microinjection molding process to reduce cost. Aluminum mold inserts were diamond machined by the slow tool servo method. The performance of the compound eye was tested using a home-built optical setup. The images captured demonstrate that the proposed structures can successfully steer images from a curved surface onto a planar photoreceptor. Experimental results show that the compound eye in this research has a field of view of 87°. In addition, images formed by multiple channels were found to be evenly distributed on the flat photoreceptor. Additionally, overlapping views of the adjacent channels allow higher resolution images to be re-constructed from multiple 3D images taken simultaneously.