Involvement of TNF-α, NF-κB, and Fas Signaling Pathways in the Pathogenesis of Certain Diseases of the Nervous System

Abstract Despite the diverse etiologies of central nervous system (CNS) diseases, such as ischemic stroke, Parkinson’s disease, Alzheimer’s disease, schizophrenia, and epilepsy, these conditions share common mechanisms, biochemical pathways, and processes. These include neuroinflammation and neuronal death, mediated by various molecules, including cytokines. Cytokines are key mediators involved in the regulation of various immune and inflammatory processes and serve as biomarkers for many diseases. Cytokines and related molecules form a complex network that modulates the immune system, exerting a wide range of influences on its functions. The aim of this study was to analyze the involvement of cytokines and related molecules in the pathogenesis of CNS diseases, both acute (stroke) and chronic neurodegenerative diseases, including Parkinson’s disease, Alzheimer’s disease, and epilepsy. This article examines the key functions and roles of the TNF-α, NF-κB, and Fas signaling pathways in the pathogenesis of the most common CNS diseases. These molecules can serve as biomarkers for acute and chronic CNS diseases and play an important role in diagnosis and prognosis. While TNF-α inhibition has been shown to yield beneficial results in some diseases, conflicting data have been obtained for Alzheimer’s disease, Parkinson’s disease, and epilepsy due to the activation of different pro- and anti-inflammatory cascades depending on TNFR1 or TNFR2 receptor binding. The use of highly selective NF-κB inhibitors leads to varying, mostly positive, results depending on the disease. Inhibition of Fas with monoclonal antibodies has shown significant results in the treatment of cancer and autoimmune diseases. Thus, TNF-α, NF-κB and Fas, as well as their adapter molecules, appear to be promising therapeutic targets for the treatment of nervous system diseases of various etiologies.