Gulf War Illness (GWI) encompasses various neuromuscular symptoms. Several studies have been conducted so far to delineate the cause of these symptoms, but as of yet, treatment strategies have been unsatisfactory. We hypothesize that the repetitive exposures to various chemicals, even at non-lethal doses can inhibit acetylcholinesterace (AChE) irreversibly. Prophylactic treatments with reversible AChE inhibitors such as pyridostigmine bromide, anti-nerve gas pills, anti-inflammatory glucocorticoids, corticosterone, insect repellents like DEET and various vaccines not only prime the immune system, but paradoxically trigger the CNS-glymphatic system to mount neuroinflammatory response in some individuals. There are complex networks of trophic factors that are secreted to maintain the neurons both in the CNS and PNS. These support the growth, survival, synaptic plasticity and differentiation of both developing and mature neurons by signaling through tyrosine kinases that are receptor specific These neurotrophic factors are essential for axon growth and regeneration of injured neurons. They are directly associated with the formation and modulation of short and long-term memories, since nothing in our system exists independently. The other factors that are associated to influence the brain parenchyma are the neuropoietic cytokines, matrix metalloproteinase and complement components. These factors play a crucial role in restoration of the function of injured neurons. Any damage to the peripheral nerve results in a rapid upregulation of these factors at the proximal and distal stump where macrophages invade. If the clearance is not rapid, we suspect that prolonged presence of these proteins could elicit immune response by activating T and B Cells in some of the GWI patients as a result may have the continued presence of autoantibodies in their blood stream. Any modulations in these factors can elicit sub-clinical symptoms that can go unnoticed for several years but initiate altered immune response.
My scientific interest involves an integrated approach to understanding the mechanism of disease susceptibility. My primary training was in Immunology and Immunogenetics; my post-doctoral training in various fields of study exposed me in-depth to various fields viz., cardiology, pulmonary, gastroenterology, nephrology, dermatology, ophthalmology, and neurology with the focus on the immune surveillance and the resulting immune response. There are many unique factors govern the functioning of each organ. My interest is to examine the underlying factors associated with environmental exposures as the leading cause for neurodegenerative diseases especially focusing on the redox signaling that change the interaction of proteins, with other intercellular and intracellular proteins, chromatin (DNA, RNA), phospholipids, enzymes, mitochondria, exosomes and drugs initiating subtle changes at the receptor level. This progressively affects the physiological functions of the body, resulting in disease manifestation. Understanding the key regulators will help in designing appropriate therapeutics using predictive biomarkers.