Delineating the Neuroinflammatory Crosstalk in Neurodegeneration and Probing the Near Future Therapeutics

Abstract

Neurodegenerative disorders are threatening mankind with significant health and economic burden. Neurodegeneration involves the deterioration of neurons in the central nervous system (CNS), resulting in decreased neuronal survival. Therefore, it is of utmost requirement to develop a promising pharmacological strategy to minimize or prevent the progression of the underlying disease pathogenesis. In neurodegenerative disease conditions, neurons and glial cells present in the specific brain regions are damaged and depraved, resulting in specified disease symptoms in the patients. Neuroinflammation plays a major role in the degeneration of neuronal cells by regulating the expression of interleukin-1 beta (IL-1β), IL-6, IL-8, IL-33, tumor necrosis factor-alpha (TNF-α), chemokines Cxcl3 (C-C motif) ligand 2 (CCL2), CXCL5, granulocyte-macrophage colony-stimulating factor (GM-CSF), glia maturation factor (GMF), substance P, reactive oxygen species (ROS), reactive nitrogen species (RNS), impaired tuning of immune cells and nuclear factor kappa-B (NF-κB). Considering this, it is very important to understand the in-depth role of neuroinflammation in the initiation and progression of various neurodegenerative diseases, including Alzheimer's Disease (AD), Parkinson's Disease (PD), Huntington's Disease (HD), as well as Multiple Sclerosis (MS). Recent shreds of evidence have suggested that using exogenous ligands to approach various biological molecules or cellular functioning that modulates the neuroinflammation, such as microglia response, P2X7 receptors, TLR receptors, oxidative stress, PPARγ, NF-κB signaling pathway, NLRP3 inflammasome, caspase-1 signaling pathway, and mitochondrial dysfunction, helps to combat neurodegeneration in a variety of diseases. Thus, targeting the neuroinflammatory drive could provide a beacon for the management of neurodegenerative diseases. Here, we have attempted to provide comprehensive literature suggesting the role of neuroinflammation in neurodegeneration and its implication in the development of near-future neurotherapeutics.