Page - (000280) - in Biomedical Chemistry: Current Trends and Developments

more “docking” sites for new AMPA receptors from nearby locations. In the end, the result of controlled calcium entry into a synaptic spine is more AMPA receptors that are more permeable to cations. Of course, protein phosphatases can act to reverse these potentiation modifications to return the synapses to the pre-LTP levels. Besides direct activation of postsynaptic kinases, calcium entry can activate a second messenger cascade to turn on gene transcription of proteins such as CaMKII and PKAII leading to relatively high local concentrations of these kinases in the synaptic spine. Both of these kinases have been found to play a role in LTP processes, such as spine volume, addition of new AMPA receptors, and direct phosphorylation of ion channels. It is this local effect of LTP that allows for selective potentiation of single synapses and, because of this, each synaptic spine could be considered isolated from other postsynaptic zones as all of the changes in kinase activity are highly restricted to that local spine. This addressable and highly spatial system is likely related to long-term memory storage. 3.2.4 Excitotoxicity A common molecular mechanism in both acute and chronic neurodegenerative diseases including stroke, Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis, multiple sclerosis, and others is the excitotoxic loss of dendritic synaptic spines and eventual neuronal death. Dendritic synaptic spines are the postsynaptic regions of a neuron that receive the chemical signal from the presynaptic cell, in this case via glutamate diffusion. These spines are essential to brain function, such as memory formation and related neural plasticity mechanisms. Pruning or loss of synaptic spines may occur through misdirected voltage- or ligand-gated ion channels. The excitotoxic effects of calcium have long been thought to be due to excess quantities of calcium, but evidence is accumulating that the route by which calcium enters the cell may be at least as important (Szydlowska & Tymianski, 2010). Recent research suggests that in Huntington’s disease, a neurodegenerative disorder, calcium entering neurons via