| First Author | Alfonso S | Year | 2014 |
| Journal | Eur J Neurosci | Volume | 39 |
| Issue | 7 | Pages | 1225-33 |
| PubMed ID | 24713001 | Mgi Jnum | J:228485 |
| Mgi Id | MGI:5707143 | Doi | 10.1111/ejn.12499 |
| Citation | Alfonso S, et al. (2014) Synapto-depressive effects of amyloid beta require PICK1. Eur J Neurosci 39(7):1225-33 |
| abstractText | Amyloid beta (Abeta), 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 Abeta weakens synapses is not well understood. Here we showed that the PDZ domain protein, protein interacting with C kinase 1 (PICK1), was required for Abeta to weaken synapses. In mice lacking PICK1, elevations of Abeta failed to depress synaptic transmission in cultured brain slices. In dissociated cultured neurons, Abeta failed to reduce surface alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunit 2, a subunit of alpha-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 Abeta on synapses and surface receptors. We concluded that GluA2-PICK1 interactions are a key component of the effects of Abeta on synapses. |
