Cyclisation of Cell-Penetrating PDZ-Binding Peptides Directed to PSD95

Excitatory glutamatergic neurotransmission via N-methyl-D-aspartate receptor (NMDAR) is critical for synaptic plasticity and survival of neurons. Excessive NMDAR activity, however can cause excitotoxicity and promote cell death, underlying a potential mechanism of neurodegeneration occurring in Alzheimer’s disease (AD). The regulation of calcium levels at synapses is important for pre- and post-synaptic activation in the hippocampus, where glutamate is the primary neurotransmitter, acting via metabotropic and ionotropic receptors.