ll Center for Research in Neuroscience

Montréal, Canada

ll Center for Research in Neuroscience

Montréal, Canada

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PubMed | McGill University, Humboldt University of Berlin, Max Planck Institute for Molecular Genetics, Charité - Medical University of Berlin and 3 more.
Type: | Journal: Scientific reports | Year: 2015

The amyloid-42 (A42) peptide is believed to be the main culprit in the pathogenesis of Alzheimer disease (AD), impairing synaptic function and initiating neuronal degeneration. Soluble A42 oligomers are highly toxic and contribute to progressive neuronal dysfunction, loss of synaptic spine density, and affect long-term potentiation (LTP). We have characterized a short, L-amino acid A-oligomer Interacting Peptide (AIP) that targets a relatively well-defined population of low-n A42 oligomers, rather than simply inhibiting the aggregation of A monomers into oligomers. Our data show that AIP diminishes the loss of A42-induced synaptic spine density and rescues LTP in organotypic hippocampal slice cultures. Notably, the AIP enantiomer (comprised of D-amino acids) attenuated the rough-eye phenotype in a transgenic A42 fly model and significantly improved the function of photoreceptors of these flies in electroretinography tests. Overall, our results indicate that specifically trapping low-n oligomers provides a novel strategy for toxic A42-oligomer recognition and removal.


Yu L.,ll Center for Research in Neuroscience | Zhou Y.,McGill University | Cheng S.,ll Center for Research in Neuroscience | Rao Y.,ll Center for Research in Neuroscience
Journal of Neuroscience | Year: 2010

While it is well established that Semaphorin family proteins function as axon guidance ligands in invertebrates and vertebrates, several recent studies indicate that the Drosophila Semaphorin-1a (Sema1a), a transmembrane Semaphorin, can also function as a receptor during neural development. The regulator of Sema1a reverse signaling, however, remains unknown. In this study, we show that like Sema1a, the well known Semaphorin receptor Plexin A (PlexA), is required for the proper guidance of photoreceptor (R cell) axons in the Drosophila visual system. Loss of PlexA, like loss of semala, disrupted the association of R-cell growth cones in the optic lobe. Conversely, overexpression of PlexA, like overexpression of sema1a, induced the hyperfasciculation of R-cell axons. Unlike Sema1a, however, the cytoplasmic domain of PlexA is dispensable. Epistasis analysis suggests that PlexA functions upstream of semala. And PlexA and sema1a interact genetically with Rho1. We propose that PlexA regulates Semala reverse signaling in the Drosophila visual system. Copyright © 2010 the authors.

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