SUMOylation (small ubiquitin-like modifier conjugation) is an important post-translational modification which is becoming increasingly implicated in the altered protein dynamics associated with brain ischemia. The function of SUMOylation in cells undergoing ischemic stress and the identity of small ubiquitin-like modifier (SUMO) targets remain in most cases unknown. However, the emerging consensus is that SUMOylation of certain proteins might be part of an endogenous neuroprotective response. This review brings together the current understanding of the underlying mechanisms and downstream effects of SUMOylation in brain ischemia, including processes such as autophagy, mitophagy and oxidative stress. We focus on recent advances and controversies regarding key central nervous system proteins, including those associated with the nucleus, cytoplasm and plasma membrane, such as glucose transporters (GLUT1, GLUT4), excitatory amino acid transporter 2 glutamate transporters, K + channels (K2P1, K v 1.5, K v 2.1), GluK2 kainate receptors, mGluR8 glutamate receptors and CB1 cannabinoid receptors, which are reported to be SUMO-modified. A discussion of the roles of these molecular targets for SUMOylation could play following an ischemic event, particularly with respect to their potential neuroprotective impact in brain ischemia, is proposed. Keywords: ion channel, neurodegeneration, receptor, small ubiquitin-like modifier, stroke, transporter. Post-translational modifications are critical events in signaling cascades that enable cells to efficiently, rapidly and reversibly respond to extracellular stimuli. This is particularly important in the CNS, where extremely complex and finely tuned processes, such as synaptic communication, take place. Apart from playing a key physiological role, posttranslational modifications, such as the well-characterized phosphorylation and ubiquitynation processes, mediate the synaptic dysfunction and neuronal death occurring in neurodegenerative diseases. SUMOylation, which involves the covalent attachment of the 97-amino acid small ubiquitinlike modifier (SUMO) protein, has been shown to be crucial for cell viability and to be activated in the post-ischemic brain (reviewed in Yang et al. 2008a). We update this topic by focusing on key molecular targets for SUMOylation that could play a potential neuroprotective role following an ischemic event.Although the exact function of SUMOylation and the identity of disease-modified SUMO targets remain largely unknown, evidence supports the involvement of SUMOylation in an endogenous neuroprotective response (Lee et al. 2007(Lee et al. , 2009bDatwyler et al. 2011;Cimarosti et al. 2012). Given the neuroprotective potential of SUMOylation in brain ischemia, it is tempting to speculate that a detailed investigation into the specific disease-modified SUMO targets, as well as the underlying mechanisms and pathways, may identify new molecular targets for future drug discovery. Here, we briefly review the current studies investigating the roles of S...

Differentiated human neural stem cells were cultured in an inert three-dimensional (3D) scaffold and, unlike two-dimensional (2D) but otherwise comparable monolayer cultures, formed spontaneously active, functional neuronal networks that responded reproducibly and predictably to conventional pharmacological treatments to reveal functional, glutamatergic synapses. Immunocytochemical and electron microscopy analysis revealed a neuronal and glial population, where markers of neuronal maturity were observed in the former. Oligonucleotide microarray analysis revealed substantial differences in gene expression conferred by culturing in a 3D vs a 2D environment. Notable and numerous differences were seen in genes coding for neuronal function, the extracellular matrix and cytoskeleton. In addition to producing functional networks, differentiated human neural stem cells grown in inert scaffolds offer several significant advantages over conventional 2D monolayers. These advantages include cost savings and improved physiological relevance, which make them better suited for use in the pharmacological and toxicological assays required for development of stem cell-based treatments and the reduction of animal use in medical research. Copyright © 2015 John Wiley & Sons, Ltd.

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