Increased Post-Translational Lysine Acetylation of Myelin Basic Protein Is Associated with Peak Neurological Disability in a Mouse Experimental Autoimmune Encephalomyelitis Model of Multiple SclerosisClick to copy article linkArticle link copied!
- Ryan Lillico
- Ting Zhou
- Tina Khorshid Ahmad
- Nicholas Stesco
- Kiana Gozda
- Jessica Truong
- Jiming Kong
- Ted M. Lakowski
- Michael Namaka
Abstract

Citrullination of arginine residues is a post-translational modification (PTM) found on myelin basic protein (MBP), which neutralizes MBPs positive charge, and is implicated in myelin damage and multiple sclerosis (MS). Here we identify lysine acetylation as another neutralizing PTM to MBP that may be involved in myelin damage. We quantify changes in lysine and arginine PTMs on MBP derived from mice induced with an experimental autoimmune encephalomyelitis (EAE) model of MS using liquid chromatography tandem mass spectrometry. The changes in PTMs are correlated to changes in neurological disability scoring (NDS), as a marker of myelin damage. We found that lysine acetylation increased by 2-fold on MBP during peak NDS post-EAE induction. We also found that mono- and dimethyl-lysine, as well as asymmetric dimethyl-arginine residues on MBP were elevated at peak EAE disability. These findings suggest that the acetylation and methylation of lysine on MBP are PTMs associated with the neurological disability produced by EAE. Since histone deacetylase (HDAC) inhibitors have been previously shown to improve neurological disability, we also show that treatment with trichostatin A (a HDAC inhibitor) improves the NDS of EAE mice but does not change MBP acetylation.
Cited By
Smart citations by scite.ai include citation statements extracted from the full text of the citing article. The number of the statements may be higher than the number of citations provided by ACS Publications if one paper cites another multiple times or lower if scite has not yet processed some of the citing articles.
This article is cited by 12 publications.
- Kumar D. Shanmukha, Harikrishnareddy Paluvai, Santosh K. Lomada, Mahesh Gokara, Suresh K. Kalangi. Histone deacetylase (HDACs) inhibitors: Clinical applications. 2023, 119-152. https://doi.org/10.1016/bs.pmbts.2023.02.011
- Anna Fontana, Ilaria Cursaro, Gabriele Carullo, Sandra Gemma, Stefania Butini, Giuseppe Campiani. A Therapeutic Perspective of HDAC8 in Different Diseases: An Overview of Selective Inhibitors. International Journal of Molecular Sciences 2022, 23
(17)
, 10014. https://doi.org/10.3390/ijms231710014
- Xiuying Lv, Mi Zhou, Qi Zhang, Yan He, Ying Wang, Jingxiu Xuan, Guixiu Shi, Yan Li. Abnormal Histones Acetylation in Patients with Primary Sjögren's Syndrome. Clinical Rheumatology 2022, 41
(5)
, 1465-1472. https://doi.org/10.1007/s10067-021-06036-4
- Licia C. Silva-Costa, Bradley J. Smith. Post-translational Modifications in Brain Diseases: A Future for Biomarkers. 2022, 129-141. https://doi.org/10.1007/978-3-031-05460-0_10
- Y. Liu, Z. Ye, J. Hu, Z. Xiao, F. Zhang, X. Yang, W. Chen, Y. Fu, D. Cao. White Matter Alterations in Spastic Paraplegia Type 5: A Multiparametric Structural MRI Study and Correlations with Biochemical Measurements. American Journal of Neuroradiology 2022, 43
(1)
, 56-62. https://doi.org/10.3174/ajnr.A7344
- Daniela Buonvicino, Giuseppe Ranieri, Alberto Chiarugi. Treatment with Non-specific HDAC Inhibitors Administered after Disease Onset does not Delay Evolution in a Mouse Model of Progressive Multiple Sclerosis. Neuroscience 2021, 465 , 38-45. https://doi.org/10.1016/j.neuroscience.2021.04.002
- Yu Zhang, Yiqiong Yang, Xiuxiu Hu, Zhi Wang, Li Li, Pingsheng Chen. PADs in cancer: Current and future. Biochimica et Biophysica Acta (BBA) - Reviews on Cancer 2021, 1875
(1)
, 188492. https://doi.org/10.1016/j.bbcan.2020.188492
- Surabhi Shukla, Babu L. Tekwani. Histone Deacetylases Inhibitors in Neurodegenerative Diseases, Neuroprotection and Neuronal Differentiation. Frontiers in Pharmacology 2020, 11 https://doi.org/10.3389/fphar.2020.00537
- Yeny Acosta-Ampudia, Diana M. Monsalve, Carolina Ramírez-Santana. Identifying the culprits in neurological autoimmune diseases. Journal of Translational Autoimmunity 2019, 2 , 100015. https://doi.org/10.1016/j.jtauto.2019.100015
- Vaibhav Singh, Ajai Tripathi, Ranjan Dutta. Proteomic Approaches to Decipher Mechanisms Underlying Pathogenesis in Multiple Sclerosis Patients. PROTEOMICS 2019, 19
(16)
https://doi.org/10.1002/pmic.201800335
- Lei Sun, Elphine Telles, Molly Karl, Fengdong Cheng, Noreen Luetteke, Eduardo M Sotomayor, Robert H Miller, Edward Seto. Loss of HDAC11 ameliorates clinical symptoms in a multiple sclerosis mouse model. Life Science Alliance 2018, 1
(5)
, e201800039. https://doi.org/10.26508/lsa.201800039
- Hao Qiu, Yanzhi Guo, Lezheng Yu, Xuemei Pu, Menglong Li. Predicting protein lysine methylation sites by incorporating single-residue structural features into Chou's pseudo components. Chemometrics and Intelligent Laboratory Systems 2018, 179 , 31-38. https://doi.org/10.1016/j.chemolab.2018.05.007
Article Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.
Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.
The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated.