Please login first
Comprehensive investigation of dysregulated gene expression in MS CSF lymphocytes reveals novel insights on disease pathology, population risk, and treatment
1  Phillips Exeter Academy, Pioneer Research Institute, North Andover, Massachusetts 01845, United States
Academic Editor: Grazyna Lietzau

Abstract:

Multiple sclerosis (MS) is an autoimmune disease that produces a complex range of symptoms including movement trouble, cognitive impairment, and bowel dysfunction. The disease progresses through the central nervous system (CNS), particularly the cerebrospinal fluid (CSF). Previous research suggests that CSF lymphocytes contribute significantly to disease progression, resulting in the misregulation of many genes. This thorough study examined the bulk tissue expression and single-nucleotide polymorphisms (SNPs) of 16 misregulated CSF genes. The study noted ethnic populations that are more susceptible to genetic variation along with drugs that can be used as MS treatments. The bulk tissue plots revealed a correlation between gene expression changes in the CSF and damage in the gut-associated lymphoid tissue (GALT). The SNP data further affirmed this finding with the tibial nerve—often associated with bowel damage in MS—having the most variants. Analyzing the population genetics of the collected SNPs showed that ethnic groups in Latin America and Africa were most likely to have the highest frequency in the least common alleles. Lastly, the study identified 12 drugs that regulate the dysregulated CSF genes with the vast majority being anti-cancer agents or histone deacetylase (HDAC) inhibitors. In short, discovering the effects and treatments of the misregulated CSF genes produced findings that deviate from prior MS studies. The results unveiled a much greater significance of the peripheral nervous system (PNS) and enteric nervous system (ENS), non-European susceptibility to symptoms, and drugs similar to cancer treatment.

Keywords: multiple sclerosis; cerebrospinal fluid; central nervous system; population genetics
Comments on this paper
Currently there are no comments available.


 
 
Top