On key cellular targets considered central to neurodegenerative disease development. In relation to molecular events potentially impacted by ELF-EMF, live, adult human neurons are not readily available. However, as a valuable alternative, human SH-SY5Y cells express a neuronal phenotype and represent a well characterized immortalized line that, although removed from the in vivo system, provide the opportunity to study responses in human rather than rodent neural cells. A large body of evidence supports a direct contribution of inflammation in the development and progression of neurodegeneration. In this regard, a wide range of inflammatory markers, either absent or minimally expressed in the healthly population, have been found present in AD, MS, PD, HD, ALS and MSA. Additionally, oxidative stress, marked by lipid peroxidation, nitration, reactive carbonyls, and nucleic acid oxidation, is perhaps the earliest feature of neurodegeneration and occurs in vulnerable neurons preceding any defining classical pathology. Within all aerobic cells, and particularly for highly metabolic neurons, the processes involved in energy production and respiration inevitably generate reactive oxiygen and nitrogen species, which represent a wide range of small PI-103 signaling molecules with highly reactive unpaired valence electrons. Oxidative stress occurs when ROS/RNS production exceeds the abilities of resident antioxidant defense mechanisms to sequester free radical intermediates, which consequently escape to then damage major macromolecules. For example, the presence of the reactive peroxynitrite has been observed in acute and chronic active MS lesions, and nitric oxide metabolites, lipid peroxidation products are reported significantly elevated in the serum of patients with MS. A pronounced increase in NO levels has been described in ALS, and oxidative stress is a common downstream mechanism by which nigral dopamine neurons are damaged in PD. ROS is additionally generated by the activation of several inflammatory enzymes, for example the expression of inducible nitric oxide synthase is under the transcriptional control of a variety of inflammatory cytokines, and the expression of proinflammatory mediators appears to be redox sensitive. The fine control of inflammatory mediator levels appears to be critical to neuronal homeostasis and health. As an example, a deficiency in neuronal TGF-b signaling promotes neurodegeneration and AD, whereas augmented TGF-b can act as an antiinflammatory cytokine and has potential neuroprotective action in AD and following a CNS insult. Interleukin 18 exerts proinflammatory effects by inducing gene expression and synthesis of cytokines, chemokines and adhesion molecules, whereas its natural inhibitor, IL-18 binding protein, operates as a key negative feedback mechanism to both balance and limit the impact of inflammation. Likewise, the actions of microglial cells are regulated at a number of stages, such as at the level of their movement by the monocyte chemoattractant protein. In the current study, we investigated the impact of an electromagnetic wave on SH-SY5Y cell cultures in relation to oxidative stress, with a focus on select mechanisms to balance oxidative damage and inflammation.