Synapto-depressive effects of amyloid beta require PICK1
| Autor: | Roberto Malinow, Anthone W. Dunah, Charles C. Banos, Richard L. Huganir, Kenneth J. Rhodes, Timothy R. Chan, Helmut W. Kessels, Gnanasambandam Kumaravel, Stephanie Alfonso, Edward Lin, Kevin Guckian, Robert H. Scannevin |
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| Přispěvatelé: | Netherlands Institute for Neuroscience (NIN) |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Amyloid beta
Protein subunit PDZ domain Cell Cycle Proteins Neurotransmission Hippocampus Article Synapse Mice 03 medical and health sciences 0302 clinical medicine Animals Receptors AMPA Receptor Cells Cultured 030304 developmental biology Neurons 0303 health sciences Amyloid beta-Peptides biology General Neuroscience P3 peptide Excitatory Postsynaptic Potentials Nuclear Proteins Peptide Fragments Rats 3. Good health Synapses biology.protein Carrier Proteins PICK1 Neuroscience 030217 neurology & neurosurgery Protein Binding |
| Zdroj: | The European journal of neuroscience, 39(7), 1225-33. Wiley-Blackwell |
| ISSN: | 0953-816X |
| Popis: | Amyloid beta (Aβ), a key component in the pathophysiology of Alzheimer's disease, is thought to target excitatory synapses early in the disease. However, the mechanism by which Aβ weakens synapses is not well understood. Here we showed that the PDZ domain protein, protein interacting with C kinase 1 (PICK1), was required for Aβ to weaken synapses. In mice lacking PICK1, elevations of Aβ failed to depress synaptic transmission in cultured brain slices. In dissociated cultured neurons, Aβ failed to reduce surface α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunit 2, a subunit of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors that binds with PICK1 through a PDZ ligand-domain interaction. Lastly, a novel small molecule (BIO922) discovered through structure-based drug design that targets the specific interactions between GluA2 and PICK1 blocked the effects of Aβ on synapses and surface receptors. We concluded that GluA2-PICK1 interactions are a key component of the effects of Aβ on synapses. |
| Databáze: | OpenAIRE |
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