Kerri Cobb
kac1000@wildcats.unh.edu


The purpose of this research is to gain further understanding of multiple sclerosis and to gain a better understanding of the IL23A gene, which plays key roles in development of multiple sclerosis. Current literature on multiple sclerosis was reviewed, and research was performed using bioinformatic tools. In this research, the gene that is the primary focus is the IL23A gene. Results from various research show that the IL23A gene is associated with the risk of multiple sclerosis. The cytokine IL23A has significant effects in the differentiation of pro-inflammatory cells, and these cells have been deemed to be the key factors in the pathogenesis of MS.Since functional genetic variants within the IL23A gene have important impacts on the host immune response, they could be good candidates as a focus for genetic association studies.


Introduction

Multiple sclerosis (MS) is a chronic immune-mediated disorder of the central nervous system (Koudriavtseva, T. & Mainero, C., 2016). It is characterized by neuroinflammation, neurodegeneration, demyelination, and death of neurons. The destruction occurs in the myelin sheath, which surrounds the axon of nerve cells, and facilitates the transmission of nerve impulses. Once the neurons of the Central Nervous System (CNS) are damaged, they are unable to regenerate the way that other cells in the body can. The purpose of this article is to discuss the possible factors involved in Multiple Sclerosis.
Inflammation is a defense mechanism of the body that functions to repair, regenerate, and remove damaged cells, infective agents, toxins, or parasites from the body (Kempuraj et al., 2016). The immune and inflammatory cells that carry out inflammatory responses include T-cells, neutrophils, macrophages, microglia, and mast cells. Neuroinflammation is a defense mechanism that specifically restores the damaged glial cells and neuronal cells in the CNS.Initially, Neuroinflammation is a response that protects the brain, but excess inflammatory responses are harmful, and inhibit neuronal regeneration. Factors that can initiate neuroinflammation in the CNS include ageing, dementia, trauma, stroke, hypertension, depression, diabetes, tumors, infections, toxins, and drugs (Kempuraj et al., 2016).

Neurodegeneration is a condition in which the structure and functions of neurons are changed, which leads to reduced neuronal survival and increased death of neurons in the CNS (Kempuraj et al., 2016). Inflammatory and neurotoxic mediators mediate neurodegeneration. Inflammatory mediators are released by activated microglia, astrocytes, neurons, T-cells, and mast cells.Immune cells, inflammatory cells, and inflammatory mediators cross the defective blood-brain-barrier (BBB) and add to neuroinflammation. Though inflammation is an important factor in the onset and the progression of neurodegenerative diseases such as MS, anti-inflammatory drugs do not provide significant therapeutic effects in MS patients (Kempuraj et al., 2016). The production and development of the disease is not yet clearly understood.

Interleukin-23A (IL23A) regulates and coordinates immune cell activities by interacting with its receptor IL23R (Li et al., 2016). It holds important responsibilities in the pathogenesis of immune inflammatory diseases. Multiple sclerosis may include IL23A in the pathogenesis. IL-23A is involved in chronic or autoimmune inflammations, by supporting the Th17 cells. IL-23A also plays a key role in mediating several other autoimmune inflammation diseases, such as those in the colon and brain. When combined with the heterodimeric receptor, which comprises interleukin-23A receptor (IL-23R) and interleukin 12 receptor beta 1 (IL-12RB1), IL-23A carries out its functions and cells responding to the IL-23A signal are mainly determined by their expression of IL-23R (Li et al., 2016).Multiple variants in the IL-23R gene have been reported to be associated with human autoimmune disorders, such as inflammatory bowel disease and psoriasis. A previous study was reviewed which analyzed the transcribed regions and splicing sites of the genes coding for IL23A and its receptors IL23R and IL12RB1 and compared 206 Chinese Han inflammatory demyelinating diseases (including 84 MS) and 300 controls (Li et al., 2016). The previous study also compared the serum levels of IL-23A in different genotype groups of the patients.


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