Could the Heat Shock Proteins 70 Family Members Exacerbate the Immune Response in Multiple Sclerosis? An in Silico Study.

Luigi Chiricosta,Placido Bramanti,Emanuela Mazzon,Agnese Gugliandolo

doi:10.3390/genes11060615

Luigi Chiricosta, Placido Bramanti + Show 2 more

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https://doi.org/10.3390/genes11060615

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Journal: Genes	Publication Date: Jun 3, 2020
Citations: 19	License type: CC BY 4.0

Affiliation: Centro Neurolesi Bonino Pulejo

Abstract

Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease of the central nervous system. It represents one of the main causes of neurological disability in young people. In MS, the autoimmune response is directed against myelin antigens but other possible bio-molecular markers are investigated. The aim of this work was, through an in silico study, the evaluation of the transcriptional modifications between healthy subjects and MS patients in six brain areas (corpus callosum, hippocampus, internal capsule, optic chiasm, frontal and parietal cortex) in order to identify genes representative of the disease. Our results show the upregulation of the Heat Shock Proteins (HSPs) HSPA1A, HSPA1B, HSPA7, HSPA6, HSPH1 and HSPA4L of the HSP70 family, among which HSPA1A and HSPA1B are upregulated in all the brain areas. HSP70s are molecular chaperones indispensable for protein folding, recently associated with immune system maintenance. The little overexpression of the HSPs protects the cells from stress but extreme upregulation can contribute to the MS pathogenesis. We also investigated the genes involved in the immune system that result in overall upregulation in the corpus callosum, hippocampus, internal capsule, optic chiasm and are absent in the cortex. Interestingly, the genes of the immune system and the HSP70s have comparable levels of expression.

Highlights

Multiple sclerosis (MS) is a chronic autoimmune disorder that affects the central nervous system (CNS)
Instead of focusing on polymorphisms, we investigated the expression of the genes that encode for the HSP70s for all six brain areas that we studied (Table 1)
Our results show that all the brain areas that we studied—corpus callosum, hippocampus, optic chiasm, internal capsule, frontal cortex and parietal cortex—overexpress both HSPA1A and HSPA1B

Summary

Introduction

Multiple sclerosis (MS) is a chronic autoimmune disorder that affects the central nervous system (CNS). The disease course can be different between individual patients. MS (RRMS), secondary progressive MS (SPMS), primary progressive MS (PPMS). The development of permanent neurological deficits and the progression of clinical disability become prominent, leading to SPMS. PPMS is present only in a minority of patients that show a progressive disease course since MS onset [1]. The cause of MS is not completely clear, but a multifactorial cause is accepted, where genetic as well as environmental factors may influence the individual disease risk in a complex manner that is not fully clarified. An early treatment of MS is necessary to limit the permanent damage to the CNS. Disease-modifying therapies are considered as standard treatments for MS, and their safety profile is considered to be acceptable [2]

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