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

Overview

Journal Genes (Basel)

Publisher MDPI

Date 2020 Jun 7

PMID 32503176

Citations 11

Authors

Luigi Chiricosta

Agnese Gugliandolo

Placido Bramanti

Emanuela Mazzon

Affiliations

Soon will be listed here.

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) , , , , and of the HSP70 family, among which and 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.

Citing Articles

Integrative Analyses of Single-Cell RNA-Sequencing and Bulk RNA-Sequencing Reveal Prognostic Markers of Peripheral Blood Mononuclear Cells in Patients with Cardiogenic Shock Receiving Venous-Arterial Extracorporeal Membrane Oxygenation Support....

Wang L, Zhong G, Chen L ACS Omega. 2025; 10(1):637-654.

PMID: 39829552 PMC: 11739955. DOI: 10.1021/acsomega.4c07339.

Putative Roles and Therapeutic Potential of the Chaperone System in Amyotrophic Lateral Sclerosis and Multiple Sclerosis.

Noori L, Saqagandomabadi V, Di Felice V, David S, Caruso Bavisotto C, Bucchieri F Cells. 2024; 13(3.

PMID: 38334609 PMC: 10854686. DOI: 10.3390/cells13030217.

subsp. Antigens Elicit a Strong IgG4 Response in Patients with Multiple Sclerosis and Exacerbate Experimental Autoimmune Encephalomyelitis.

Cossu D, Tomizawa Y, Yokoyama K, Sakanishi T, Momotani E, Sechi L Life (Basel). 2023; 13(7).

PMID: 37511812 PMC: 10381415. DOI: 10.3390/life13071437.

Role of Ganetespib, an HSP90 Inhibitor, in Cancer Therapy: From Molecular Mechanisms to Clinical Practice.

Youssef M, Cavalu S, Hasan A, Yahya G, Abd-Eldayem M, Saber S Int J Mol Sci. 2023; 24(5).

PMID: 36902446 PMC: 10002602. DOI: 10.3390/ijms24055014.

A Comprehensive Exploration of the Transcriptomic Landscape in Multiple Sclerosis: A Systematic Review.

Chiricosta L, Blando S, DAngiolini S, Gugliandolo A, Mazzon E Int J Mol Sci. 2023; 24(2).

PMID: 36674968 PMC: 9862618. DOI: 10.3390/ijms24021448.

References

Regis G, Conti L, Boselli D, Novelli F . IFNgammaR2 trafficking tunes IFNgamma-STAT1 signaling in T lymphocytes. Trends Immunol. 2005; 27(2):96-101. DOI: 10.1016/j.it.2005.12.002. View

Gehring T, Seeholzer T, Krappmann D . BCL10 - Bridging CARDs to Immune Activation. Front Immunol. 2018; 9:1539. PMC: 6039553. DOI: 10.3389/fimmu.2018.01539. View

Cui D, Wang J, Zeng Y, Rao L, Chen H, Li W . Generating hESCs with reduced immunogenicity by disrupting TAP1 or TAPBP. Biosci Biotechnol Biochem. 2016; 80(8):1484-91. DOI: 10.1080/09168451.2016.1165601. View

Leinonen R, Sugawara H, Shumway M . The sequence read archive. Nucleic Acids Res. 2010; 39(Database issue):D19-21. PMC: 3013647. DOI: 10.1093/nar/gkq1019. View

Kern F, Stanika R, Sarg B, Offterdinger M, Hess D, Obermair G . Nogo-A couples with Apg-1 through interaction and co-ordinate expression under hypoxic and oxidative stress. Biochem J. 2013; 455(2):217-27. PMC: 3806365. DOI: 10.1042/BJ20130579. View

Raska M, Weigl E . Heat shock proteins in autoimmune diseases. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2006; 149(2):243-9. DOI: 10.5507/bp.2005.033. View

Dobin A, Davis C, Schlesinger F, Drenkow J, Zaleski C, Jha S . STAR: ultrafast universal RNA-seq aligner. Bioinformatics. 2012; 29(1):15-21. PMC: 3530905. DOI: 10.1093/bioinformatics/bts635. View

Greer J . The Role of HLA in MS Susceptibility and Phenotype. Curr Top Behav Neurosci. 2014; 26:1-27. DOI: 10.1007/7854_2014_357. View

Mansilla M, Montalban X, Espejo C . Heat shock protein 70: roles in multiple sclerosis. Mol Med. 2012; 18:1018-28. PMC: 3459486. DOI: 10.2119/molmed.2012.00119. View

10.

Voskuhl R, Itoh N, Tassoni A, Matsukawa M, Ren E, Tse V . Gene expression in oligodendrocytes during remyelination reveals cholesterol homeostasis as a therapeutic target in multiple sclerosis. Proc Natl Acad Sci U S A. 2019; 116(20):10130-10139. PMC: 6525478. DOI: 10.1073/pnas.1821306116. View

11.

. Database resources of the National Center for Biotechnology Information. Nucleic Acids Res. 2017; 46(D1):D8-D13. PMC: 5753372. DOI: 10.1093/nar/gkx1095. View

12.

Anders S, Pyl P, Huber W . HTSeq--a Python framework to work with high-throughput sequencing data. Bioinformatics. 2014; 31(2):166-9. PMC: 4287950. DOI: 10.1093/bioinformatics/btu638. View

13.

Filippi M, Bar-Or A, Piehl F, Preziosa P, Solari A, Vukusic S . Multiple sclerosis. Nat Rev Dis Primers. 2018; 4(1):43. DOI: 10.1038/s41572-018-0041-4. View

14.

Conze D, Krahl T, Kennedy N, Weiss L, Lumsden J, Hess P . c-Jun NH(2)-terminal kinase (JNK)1 and JNK2 have distinct roles in CD8(+) T cell activation. J Exp Med. 2002; 195(7):811-23. PMC: 2193724. DOI: 10.1084/jem.20011508. View

15.

Niino M, Kikuchi S, Fukazawa T, Yabe I, Sasaki H, Tashiro K . Heat shock protein 70 gene polymorphism in Japanese patients with multiple sclerosis. Tissue Antigens. 2001; 58(2):93-6. DOI: 10.1034/j.1399-0039.2001.580205.x. View

16.

Dragovic Z, Broadley S, Shomura Y, Bracher A, Hartl F . Molecular chaperones of the Hsp110 family act as nucleotide exchange factors of Hsp70s. EMBO J. 2006; 25(11):2519-28. PMC: 1478182. DOI: 10.1038/sj.emboj.7601138. View

17.

. Network-based multiple sclerosis pathway analysis with GWAS data from 15,000 cases and 30,000 controls. Am J Hum Genet. 2013; 92(6):854-65. PMC: 3958952. DOI: 10.1016/j.ajhg.2013.04.019. View

18.

Richter K, Rufer A, Muller M, Burger D, Casagrande F, Grossenbacher T . Small molecule AX-024 reduces T cell proliferation independently of CD3ϵ/Nck1 interaction, which is governed by a domain swap in the Nck1-SH3.1 domain. J Biol Chem. 2020; 295(23):7849-7864. PMC: 7278359. DOI: 10.1074/jbc.RA120.012788. View

19.

Fernandez O, Alvarez-Cermeno J, Arroyo-Gonzalez R, Brieva L, Calles-Hernandez M, Casanova-Estruch B . Review of the novelties presented at the 27th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) (I). Rev Neurol. 2012; 54(11):677-91. View

20.

Turturici G, Sconzo G, Geraci F . Hsp70 and its molecular role in nervous system diseases. Biochem Res Int. 2011; 2011:618127. PMC: 3049350. DOI: 10.1155/2011/618127. View