Glutamate excitotoxicity contributes to neuronal apoptosis. Normally, glutamate is released and activates ionotropic glutamate receptors, primarily AMPA, on the post-synaptic …show more content…
By inactivating sodium-channel isoforms and decreases repetitive firing it inhibits the release of glutamate in pre-synaptic neurons (Bellingham, 2011). In higher amounts, it can block post-synaptic Ca2+-AMPA channels, which is beneficial in decreasing excitotoxicity (Van Den Bosch, Van Damme, Bogaert, and Robberecht, 2006). Nevertheless, this causes unwanted side-effects like repressing the motor neuron’s ability to propagate action potential since calcium and sodium-dependent depolarization are inhibited (Bellingham, 2011). In contrast, it activates G-protein dependent processes, releasing calcium stores to counter inhibitory effects which may consequently lead to no effects at all unless in high dosages (Bensimon, Lacomblez, and Meininger, 1994). Furthermore, aminotransferases leading to toxic levels of ammonia causing unwanted brain damage is a potential side-effect of Riluzole (Bensimon, Lacomblez, and Meininger, …show more content…
As ALS is a multi-factorial disease affecting motor neurons and surrounding cells, stem cells are used appropriately as a result of their available plasticity (Louis and Suzuki, 2014). This promotes regeneration and remodeling by reducing astrogliosis and inflammation (Teng et al., 2012). This increases the re-uptake of glutamate in order to rescue excitotoxicity (Teng et al., 2012). Studies show stem cells decreasing apoptosis through neuro-protection via growth factors to increase motor neuron strength and viability in SOD1 mutants (Louis and Suzuki, 2014).
In conclusion, glutamate excitotoxicity in ALS produces hyper-activated sodium and calcium channels as well as increased activation of Ca2+-AMPA receptors. Nevertheless, Riluzole has been able to down-regulate some of these effects. Mutant SOD1 in astrocytes contribute to glutamate excitotoxicity by inhibiting their re-uptake, but research with stem cells shows promising new ways of targeting these diseased