Label ‐free distribution of anti‐amyloid D‐AIP in Drosophila melanogaster: prevention of Aβ42‐induced toxicity without side effects in transgenic flies

We report that our small synthetic D‐amino acid Aβ42‐oligomer interacting peptide (D‐AIP) was able to rescue the toxic ‘rough eye’ phenotype induced by human Aβ42 expression in a transgen icDrosophila model without obvious side effects (i.e. high dosage of D ‐AIP does not alter overall longevity, structure or function of wildtype flies). Overall, D‐AIP provides a novel mechanism of action to reduce amyloid toxicity, thus providing a promising new prophylactic strategy to delay and/or prevent the onset of AD. AbstractSoluble oligomers of the 42 ‐amino acid amyloid beta (Aβ42) peptide are highly toxic and suspected as the causative agent of synaptic dysfunction and neuronal loss in Alzheimer's disease (AD). Previously, we have shown that a small, D‐amino acid Aβ42‐oligomer interacting peptide (D‐AIP) can neutralize human Aβ42‐m ediated toxicity usingin vitro and cell ‐based assays. In the present longitudinal study using a transgenicDrosophila melanogaster model, advanced live confocal imaging and mass spectrometry imaging (MALDI ‐MSI) showed that the eight amino acid D‐AIP can attenuate Aβ42‐induced toxicityin vivo. By separating male and female flies into distinct groups, the resultant distribution of ingested D ‐AIP was different between the sexes. The Aβ42‐induced ‘rough eye’ phenotype could be rescued in the female transgenics, likely because of the co‐localization of D‐AIP with human Aβ42 in the female fly heads. Intere...

Source: Journal of Neurochemistry - June 5, 2019 Category: Neuroscience Authors: Yifei Zhong, Adeola Shobo, Mark A. Hancock, Gerhard Multhaup Tags: Original Article Source Type: research