Review Article

Alpha-Linolenic Acid: An Omega-3 Fatty Acid with Neuroprotective Properties—Ready for Use in the Stroke Clinic?

Figure 2

Interplay between NMDA and TrkB receptors mediated by ALA-induced lipid rafts in neuronal plasma membranes. An increase in the nutraceutical ALA is hypothesized to markedly increase membrane fluidity leading to the efficient formation of lipid rafts [5] in neuronal plasma membranes. Lipid rafts are the functional domains of the plasma membrane and play a crucial role in the regulation of transmembrane signaling [6]. TrkB receptors and some NMDA receptors are constituents of lipid rafts [710] and one of the major nonprotein components of lipid rafts is cholesterol [6]. The enhanced formation and/or efficiency of transmembrane signaling is hypothesized to result in enhanced activation (phosphorylation) of NMDA and TrkB receptors via the binding of BDNF to its cognate receptor, TrkB. Activation of NMDA receptors results in enhanced calcium influx and activation of signal transduction pathways leading to activation of nuclear factor kappa B (NF-κB) via the canonical pathway (phosphorylation of I-κB leads to its dissociation from the dimer (p65/p50) which then translocates to the nucleus where it binds to κB sites to regulate gene expression) which in turn increases BDNF mRNA and protein levels [1114]. Enhanced intracellular BDNF protein expression would lead to an increase in secretion, thereby maintaining its availability to bind to TrkB in an autocrine fashion [14, 15] as well as to stimulate neurogenesis, synaptogenesis, and synaptic function at distant sites (paracrine function).