Cadmium is involved in most of the major diseases of present time that not only include cancer, heart diseases, kidney diseases but also neural diseases. Nelson et.al., in 2000, finds associations of cadmium and neural disorders between three-fold risks. They also have reported a significant trend of increasing risk for amyotrophic lateral sclerosis (ALS), a neurodegenerative disease with duration of smoking and number of cigarette pack-years. Chronic exposure to cadmium causes central nervous system disorders, like olfactory dysfunction. Cadmium released from the amygdalar neuron terminals affects the degree and balance of excitation–inhibition in synaptic neurotransmission (Minami et.al, 2000). Epidemiological studies have suggested that cadmium toxicity can be linked to neurobehavioral effects like slowing of vasomotor functioning and increase in complaints consistent with peripheral neuropathy, complaints about equilibrium, and complaints about concentration ability in a dose dependent manner (Viaene et. al., 2000). Cadmium also affects the myelinated axons in human sciatic nerve of heavy smokers, this cause myelin destruction and protrusion which clearly indicate towards the structure modulation of neural membrane. Our proposed research aims at finding out the type of proteins that are involved in these morphological and structural changes of neural membrane after cadmium exposure and whether we could prevent such phenomena with certain known derivatives like methylcobalamin or vitamin B12. Published studies have already shown that high doses of methylcobalamin are needed to regenerate neurons as well as the myelin sheath that protects nerve axons and peripheral nerves (Fontecilla et. al. 2009). Therefore, in our project we will also try to use methylcobalamin to treat the cadmium affected neural cells and we will evaluate whether we could inhibit the morphological transition and reverse it towards normal cells. Specifically this will be the first attempt to reverse the altered human nerve cell morphology towards normalcy including deciphering the signaling cascade at protein level.

Nanoparticles are being extensively used in industrial products such as catalysts, pigments, food additives, pharmaceuticals and cosmetics. Thus, human exposure to nanoparticles is inevitable and, as a result, nanotoxicology research is now gaining attention. In this work we would like to address the current deficient knowledge of cellular response to nanoparticles mainly to titanium dioxide and silver nanoparticles. Although a few studies have been carried out on the toxicity of nanoparticles with respect to cytotoxicity and oxidative stress, there are no direct reports available about their involvement in regulation of protein synthesis and effect on protein synthesis through translation regulation at various stages of protein synthesis. Titanium dioxide and silver nanoparticles have been selected for the present study as they are extensively used in air and water remediation and well as in medical and consumer products. In the medical field in particular, nanoparticles are being utilized in diagnostic and therapeutic tools to better understand, detect, and treat human diseases. Exposure to nanoparticles for medical purposes involves intentional contact or administration; therefore, understanding the properties of nanoparticles and their effect on regulation of protein synthesis through regulation at various stages of may yield new information. We will also see whether the changes in the cell shape (our preliminary observations have already confirmed this) during nanoparticles treatment may be due to smallGTPases.