Michael W Salter

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Amyloid-beta peptide is elevated in the brains of patients with Alzheimer disease and is believed to be causative in the disease process. Amyloid-beta reduces glutamatergic transmission and inhibits synaptic plasticity, although the underlying mechanisms are unknown. We found that application of amyloid-beta promoted endocytosis of NMDA receptors in(More)
N-methyl-D-aspartate receptors (NMDARs) mediate ischemic brain damage but also mediate essential neuronal excitation. To treat stroke without blocking NMDARs, we transduced neurons with peptides that disrupted the interaction of NMDARs with the postsynaptic density protein PSD-95. This procedure dissociated NMDARs from downstream neurotoxic signaling(More)
The N-methyl-D-aspartate (NMDA) receptor mediates synaptic transmission and plasticity in the central nervous system (CNS) and is regulated by tyrosine phosphorylation. In membrane patches excised from mammalian central neurons, the endogenous tyrosine kinase Src was shown to regulate the activity of NMDA channels. The action of Src required a sequence(More)
Protein-tyrosine kinases (PTKs) and protein-tyrosine phosphatases (PTPs) are key enzymes in signal-transduction pathways for a wide range of cellular processes. PTKs and PTPs are highly expressed in the central nervous system, which is consistent with the importance of tyrosine phosphorylation in neuronal function. Protein phosphorylation is known to be(More)
NMDA (N-methyl-d-aspartate) receptors (NMDARs) are a principal subtype of excitatory ligand-gated ion channel with prominent roles in physiological and disease processes in the central nervous system. Recognition that glycine potentiates NMDAR-mediated currents as well as being a requisite co-agonist of the NMDAR subtype of 'glutamate' receptor profoundly(More)
Control and treatment of chronic pain remain major clinical challenges. Progress may be facilitated by a greater understanding of the mechanisms underlying pain processing. Here we show that the calcium-sensing protein DREAM is a transcriptional repressor involved in modulating pain. dream(-/-) mice displayed markedly reduced responses in models of acute(More)
Long-term potentiation (LTP) is an activity-dependent strengthening of synaptic efficacy that is considered to be a model of learning and memory. Protein tyrosine phosphorylation is necessary to induce LTP. Here, induction of LTP in CA1 pyramidal cells of rats was prevented by blocking the tyrosine kinase Src, and Src activity was increased by stimulation(More)
Neuregulins (NRGs) and their receptors, the ErbB protein tyrosine kinases, are essential for neuronal development, but their functions in the adult CNS are unknown. We report that ErbB4 is enriched in the postsynaptic density (PSD) and associates with PSD-95. Heterologous expression of PSD-95 enhanced NRG activation of ErbB4 and MAP kinase. Conversely,(More)
Regulation of postsynaptic glutamate receptors is one of the main mechanisms for altering synaptic efficacy in the central nervous system. Recent studies have given insight into the upregulation of the NMDA receptor by Src family tyrosine kinases, which bind to scaffolding proteins in the NMDA receptor complex. Src acts as a common step in signalling(More)