Identifying and testing specific modulators of PTMs now constitute the next big challenges in order to further validate these targets and proceed towards the goal of a mechanism-based treatment for HD.”
“MAGUKs are proteins that act as key scaffolds in surface complexes containing receptors, adhesion proteins, and various signaling molecules. These complexes evolved
prior to the appearance of multicellular animals and play key roles in cell-cell intercommunication. GSK2126458 mw A major example of this is the neuronal synapse, which contains several presynaptic and postsynaptic MAGUKs including PSD-95, SAP102, SAP97, PSD-93, CASK, and MAGIs. Here, they play roles in both synaptic development and in later synaptic plasticity events. During development, MAGUKs help to organize the postsynaptic density via associations with other scaffolding proteins, such as Shank, and the actin cytoskeleton. They affect the clustering of glutamate receptors and other receptors, and these associations change with development. MAGUKs are involved in long-term potentiation and depression (e.g.,
via their phosphorylation by kinases and phosphorylation of other proteins associated with MAGUKs). Importantly, synapse development and function are dependent on the kind of MAGUK present. For example, SAP102 shows high mobility and is present in early synaptic development. Later, much of SAP102 is replaced by PSD-95, a more stable synaptic MAGUK; this is associated with changes in glutamate receptor types that SRT1720 are characteristic of synaptic maturation.”
“The emerging role of astrocytes in neural communication represents a conceptual challenge. In striking contrast to the rapid and highly space- and time-constrained machinery of neuronal spike propagation and synaptic release, astroglia appear slow and imprecise. Although a large body of independent experiments documents active signal exchange between astrocytes and neurons, some genetic models have raised doubts about the major Ca2+-dependent molecular mechanism routinely associated with release of “”gliotransmitters.”" A limited understanding of astrocytic filipin Ca2+
signaling and the imperfect compatibility between physiology and experimental manipulations seem to have contributed to this conceptual bottleneck. Experimental approaches providing mechanistic insights into the diverse mechanisms of intra-astrocyte Ca2+ signaling on the nanoscale are needed to understand Ca2+-dependent astrocytic function in vivo. This review highlights limitations and potential advantages of such approaches from the current methodological perspective.”
“Mirror neurons are a class of visuomotor neurons in the monkey premotor and parietal cortices that discharge during the execution and observation of goal-directed motor acts. They are deemed to be at the basis of primates’ social abilities. In this review, the authors provide a fresh view about two still open questions about mirror neurons.