Comparative mass spectrometry analysis of hippocampal tissue samples from patients with sclerotic and non-sclerotic temporal lobe epilepsy and nonepileptic patients was undertaken to identify differences in the levels of protein post-translational modifications (PTMs). The original proteomic data obtained by Mathoux et al. [DOI: 10.1172/jci.insight.188612] and deposited in the PRIDE repository (PXD064519) were used in this work. Our reanalysis of the comparative proteomic data identified 53 proteins with PTMs (phosphorylation, methylation, acetylation, and citrullination) that exhibited significant changes in the levels of individual modified peptides. According to the published original data, all 53 proteins are involved in processes associated with neurological diseases in general and epileptogenesis in particular. The analysis identified PTMs of proteins that could play an important role in the pathogenesis of neurological diseases.
Miroshnichenko Yu.V., Rybina A.V., Skvortsov V.S. (2025) Identification of proteins with variable levels of post-translational modifications in human temporal lobe epilepsy. Biomeditsinskaya Khimiya, 71(5), 351-363.
Miroshnichenko Yu.V. et al. Identification of proteins with variable levels of post-translational modifications in human temporal lobe epilepsy // Biomeditsinskaya Khimiya. - 2025. - V. 71. -N 5. - P. 351-363.
Miroshnichenko Yu.V. et al., "Identification of proteins with variable levels of post-translational modifications in human temporal lobe epilepsy." Biomeditsinskaya Khimiya 71.5 (2025): 351-363.
Miroshnichenko, Yu. V., Rybina, A. V., Skvortsov, V. S. (2025). Identification of proteins with variable levels of post-translational modifications in human temporal lobe epilepsy. Biomeditsinskaya Khimiya, 71(5), 351-363.
References
Skvortsov V.S., Ivanova Ya.O., Voronina A.I. (2021) The bioinformatic identification of proteins with varying levels of post-translational modifications in experimental ischemic stroke in mice. Biomeditsinskaya Khimiya, 67(6), 475–484. CrossRef Scholar google search
Voronina A.I., Miroshnichenko Yu.V., Skvortsov V.S. (2024) Bioinformatic identification of proteins with altered PTM levels in a mouse line established to study the mechanisms of the development of fibromuscular dysplasia. Biomeditsinskaya Khimiya, 70(4), 248–255. CrossRef Scholar google search
Martens L., Hermjakob H., Jones P., Adamski M., Taylor C., States D., Gevaert K., Vandekerckhove J., Apweiler R. (2005) PRIDE: the proteomics identifications database. Proteomics, 5(13), 3537–3545. CrossRef Scholar google search
Salovska B., Liu Y. (2023) Post-translational modification and phenotype. Proteomics, 23(3–4), e2200535. CrossRef Scholar google search
Yamaguchi K., Hu Y.-Y., Kawajiri K., Itakura M., Nakashima F., Shibata T., Uchida K. (2025) Adductome-based identification of lysine monomethylation as a key post-translational protein modification in autoimmune diseases. J. Biol. Chem., 301(10), 110684. CrossRef Scholar google search
Tuli L., Tsai T.-H., Varghese R.S., Xiao J.F., Cheema A., Ressom H.W. (2012) Using a spike-in experiment to evaluate analysis of LC-MS data . Proteome Sci., 10, 13. CrossRef Scholar google search
Ramazi S., Zahiri J. (2021) Posttranslational modifications in proteins: resources, tools and prediction methods. Database (Oxford), 2021, baab012. CrossRef Scholar google search
Mathoux J., Wilson M.M., Srinivas S., Litovskich G., Villalba B.L., Tran C., Kesavan J., Harnett A., Auer T., Sanz-Rodriguez A., Alkhayyat M.Kh.A.E., Sullivan M., Liu Z., Huang Y., Lacey A., Delanty N., Cryan J., Brett F.M., Farrell M.A., O'Brien D.F., Casillas-Espinosa P.M., Jimenez-Mateos E.M., Glennon J.C., Canavan M., Henshall D.C., Brennan G.P. (2025) N6-methyladenosine (m6A) dysregulation contributes to network excitability in temporal lobe epilepsy. JCI Insight, 10(14), e188612. CrossRef Scholar google search
Chen Y., Nie Q., Song T., Zou X., Li Q., Zhang P. (2025) Integrated proteomics and lipidomics analysis of hippocampus to reveal the metabolic landscape of epilepsy. ACS Omega, 10(9), 9351–9367. CrossRef Scholar google search
Ma B., Zhang K., Hendrie C., Liang C., Li M., Doherty-Kirby A., Lajoie G. (2003) PEAKS: Powerful software for peptide de novo sequencing by tandem mass spectrometry. Rapid Commun. Mass Spectrom., 17(20), 2337–2342. CrossRef Scholar google search
The UniProt Consortium (2020) UniProt: The universal protein knowledgebase in 2021. Nucleic Acids Res., 49(D1), D480–D489. CrossRef Scholar google search
Progenesis LC-MS version 4.0, Nonlinear Dynamics, Newcastle upon Tyne, UK. Scholar google search
Skvortsov V.S., Alekseychuk N.N., Miroshnichenko Yu.V., Rybina A.V. (2019) The prediction of the ion fraction of the peptide with selected charge in mass spectrometry with positive electrospray ionization. Biomedical Chemistry: Research and Methods, 2(4), e00100. CrossRef Scholar google search
Balmik A.A., Chinnathambi S. (2021) Methylation as a key regulator of Tau aggregation and neuronal health in Alzheimer's disease. Cell Commun. Signal., 19, 51. CrossRef Scholar google search
Park J.-Y., Kang T.-C. (2018) The differential roles of PEA15 phosphorylations in reactive astrogliosis and astroglial apoptosis following status epilepticus. Neurosci. Res., 137, 11–22. CrossRef Scholar google search
Chang Q., Yang H., Wang M., Wei H., Hu F. (2018) Role of microtubule-associated protein in autism spectrum disorder. Neurosci. Bull., 34(6), 1119–1126. CrossRef Scholar google search
Sanchez C., Díaz-Nido J., Avila J. (2000) Phosphorylation of microtubule-associated protein 2 (MAP2) and its relevance for the regulation of the neuronal cytoskeleton function. Prog. Neurobiol., 61(2), 133–168. CrossRef Scholar google search
Fritz D.I., Ding Y., Merrill-Skoloff G., Flaumenhaft R., Hanada T., Chishti A.H. (2023) Dematin regulates calcium mobilization, thrombosis, and early Akt activation in platelets. Mol. Cell. Biol., 43(6), 283–299. CrossRef Scholar google search
Li H., Fan S., Gong Z., Chan J.Y.K., Tong M.C.F., Chen G.G. (2024) Role of hematological and neurological expressed 1 (HN1) in human cancers. Crit. Rev. Oncol. Hematol., 201, 104446. CrossRef Scholar google search
Xin Y., Lin G., Hua T., Liang J., Sun T., Wu X. (2023) The altered expression of cytoskeletal and synaptic remodeling proteins during epilepsy. Open Life Sci., 18, 20220595. CrossRef Scholar google search
Zhang L., Feng D., Tao H., De X., Chang Q., Hu Q. (2015) Increased stathmin expression strengthens fear conditioning in epileptic rats. Biomed. Rep., 3(1), 28–32. CrossRef Scholar google search
Gozal Y.M., Seyfried N.T., Gearing M., Glass J.D., Heilman C.J., Wuu J., Duong D.M., Cheng D., Xia Q., Rees H.D., Fritz J.J., Cooper D.S., Peng J., Levey A.I., Lah J.J. (2011) Aberrant septin 11 is associated with sporadic frontotemporal lobar degeneration. Mol. Neurodegener., 6, 82. CrossRef Scholar google search
Thal D., Xavier C.-P., Rosentreter A., Linder S., Friedrichs B., Waha A., Pietsch T., Stumpf M., Noegel A., Clemen C. (2008) Expression of coronin-3 (coronin-1C) in diffuse gliomas is related to malignancy. J. Pathol., 214(4), 415–424. CrossRef Scholar google search
Kong Q., Min X., Sun R., Gao J., Liang R., Li L., Chu X. (2016) Effects of pharmacological treatments on hippocampal NCAM1 and ERK2 expression in epileptic rats with cognitive dysfunction. Oncol. Lett., 12(3), 1783–1791. CrossRef Scholar google search
Nicolay N.H., Hertle D., Boehmerle W., Heidrich F.M., Yeckel M., Ehrlich B.E. (2007) Inositol 1,4,5 trisphosphate receptor and chromogranin B are concentrated in different regions of the hippocampus. J. Neurosci. Res., 85(9), 2026–2036. CrossRef Scholar google search
Franchi F. Marte A., Corradi B., Sterlini B., Alberini G., Romei A., de Fusco A., Vogel A., Maragliano L., Baldelli P., Corradi A., Valente P., Benfenati F. (2023) The intramembrane COOH-terminal domain of PRRT2 regulates voltagedependent Na+ channels. J. Biol. Chem., 299(5), 104632. CrossRef Scholar google search
Barzasi M., Spinola A., Costa A., Pavinato L., Brusco A., Marcello E., DiLuca M., Gardoni F. (2025) Arg209Lys and Gln508His missense variants in Rabphilin 3A cause pre- and post-synaptic dysfunctions at excitatory glutamatergic synapses. Sci. Rep., 15, 8698. CrossRef Scholar google search
Zhu J.X., Aswad D.W. (2024) Isoaspartate formation and irreversible aggregation of collapsin response mediator protein 2: implications for the etiology of epilepsy and age-related cognitive decline. Amino Acids, 57, 5. CrossRef Scholar google search
Cantor J.R., Stone E.M., Chantranupong L., Georgiou G. (2009) The human asparaginase-like protein 1 hASRGL1 is an Ntn hydrolase with beta-aspartyl peptidase activity. Biochemistry, 48(46), 11026–11031. CrossRef Scholar google search
Werren E.A., Rodriguez Bey G., Majethia P., Kaur P., Patil S.J., Kekatpure M.V., Afenjar A., Qebibo L., Burglen L., Tomoum H., Demurger F., Duborg C., Siddiqui S., Tsan Y.-C., Abdullah U., Ali Z., Saadi S.M., Baig S.M., Houlden H., Maroofian R., Padiath Q.S., Bielas S.L., Shukla A. (2024) Biallelic EPB41L3 variants underlie a developmental disorder with seizures and myelination defects. Brain, 147(12), 4033–4042. CrossRef Scholar google search
Olah J., Bertrand P., Ovadi J. (2017) Role of the microtubuleassociated TPPP/p25 in Parkinson's and related diseases and its therapeutic potential. Expert Rev. Proteomics, 14(4), 301–309. CrossRef Scholar google search
Liu X.-Y., Yang J.-L., Chen L.-J., Zhang Y., Yang M.-L., Wu Y.-Y., Li F.-Q., Tang M.-H., Liang S.-F., Wei Y.-Q. (2008) Comparative proteomics and correlated signaling networkof rat hippocampus in the pilocarpine model of temporal lobe epilepsy. Proteomics, 8(3), 582–603. CrossRef Scholar google search
Singhal A., Morris V.B., Labhasetwar V., Ghorpade A. (2013) Nanoparticle-mediated catalase delivery protects human neurons from oxidative stress. Cell Death Dis., 4(11), e903. CrossRef Scholar google search
Guimarães T.G., Parmera J.B., Castro M.A.A., Cury R.G., Barbosa E.R., Kok F. (2024) X-Linked levodopa-responsive parkinsonism-epilepsy syndrome: a novel PGK1 mutation and literature review. Mov. Disord. Clin. Pract., 11(5), 556–566. CrossRef Scholar google search
Nielsen V.G., Jacobsen W.K. (2016) Iron modulates the alpha chain of fibrinogen. Biometals, 29(2), 235–238. CrossRef Scholar google search
Hernández-R J. (1992) Na+/K(+)-ATPase regulation by neurotransmitters. Neurochem. Int., 20(1), 1–10. CrossRef Scholar google search
Olrichs N.K., Mahalka A.K., Kaloyanova D., Kinnunen P.K., Bernd H.J. (2014) Golgi-associated plant pathogenesis related protein 1 (GAPR-1) forms amyloid-like fibrils by interaction with acidic phospholipids and inhibits a aggregation. Amyloid, 21(2), 88–96. CrossRef Scholar google search
Nakashima S. (2002) Protein kinase C alpha (PKC alpha): regulation and biological function. J. Biochem., 132(5), 669–675. CrossRef Scholar google search
Petersen S.L., Intlekofer K.A., Moura-Conlon P.J., Brewer D.N., del Pino Sans J., Lopez J.A. (2013) Novel progesterone receptors: neural localization and possible functions. Front. Neurosci., 7, 164. CrossRef Scholar google search
Fedotcheva T.A., Shimanovsky N.L. (2025) Neurosteroids progesterone and dehydroepiandrosterone: molecular mechanisms of action in neuroprotection and neuroinflammation. Pharmaceuticals (Basel), 18(7), 945. CrossRef Scholar google search
Huang Z., Shen S., Han X., Li W., Luo W., Lin L., Xu M., Wang Y., Huang W., Wu G., Liang G. (2023) Macrophage DCLK1 promotes atherosclerosis via binding to IKKβ and inducing inflammatory responses. EMBO Mol. Med., 15(5), e17198. CrossRef Scholar google search
Mastroeni D., Sekar S., Nolz J., Delvaux E., Lunnon K., Mill J., Liang W.S., Coleman P.D. (2017) ANK1 is up-regulated in laser captured microglia in Alzheimer's brain; the importance of addressing cellular heterogeneity. PLOS One, 12(7), e0177814. CrossRef Scholar google search
Wang X., Chen G., Wan B., Dong Z., Xue Y., Luo Q., Wang D., Lu Y., Zhu L. (2022) NRF1-mediated microglial activation triggers high-altitude cerebral edema. J. Mol. Cell Biol., 14(5), mjac036. CrossRef Scholar google search
Blondiaux A., Jia S., Annamneedi A., Çalışkan G., Nebel J., Montenegro-Venegas C., Wykes R.C., Fejtova A., Walker M.C., Stork O., Gundelfinger E.D., Dityatev A., Seidenbecher C.I. (2023) Linking epileptic phenotypes and neural extracellular matrix remodeling signatures in mouse models of epilepsy. Neurobiol. Dis., 188, 106324. CrossRef Scholar google search
Sun Z.M., Chen Q., Li M.H., Ma W.N., Zhao X.Y., Huang Z. (2019) Chronic phosphoproteomic in temporal lobe epilepsy mouse models induced by kainic acid. Beijing Da Xue Xue Bao Yi Xue Ban, 51(2), 197–205. CrossRef Scholar google search
Liu X.-B., Murray K.D. (2012) Neuronal excitability and calcium/calmodulin-dependent protein kinase type II: location, location, location. Epilepsia, 53(Suppl 1), 45–52. CrossRef Scholar google search
Cai S., Li J., Wu Y., Jiang Y.J. (2020) De novo mutations of TUBB2A cause infantile-onset epilepsy and developmental delay. Hum. Genet., 65(7), 601–608. CrossRef Scholar google search
Schoonjans A.-S., Meuwissen M., Reyniers E., Kooy F., Ceulemans B. (2016) PLCB1 epileptic encephalopathies; review and expansion of the phenotypic spectrum. Eur. J. Paediatr. Neurol., 20(3), 474–479. CrossRef Scholar google search
Fard M.K., van der Meer F., Sanchez P., Cantuti-Castelvetri L., Mandad S., Jäkel S., Fornasiero E.F., Schmitt S., Ehrlich M., Starost L., Kuhlmann T., Sergiou C., Schultz V., Wrzos C., Brück W., Urlaub H., Dimou L., Stadelmann C., Simons M. (2017) BCAS1 expression defines a population of early myelinating oligodendrocytes in multiple sclerosis lesions. Sci. Transl. Med., 9(419), eaam7816. CrossRef Scholar google search
Hu S., Tang Y., Li X., Li W., Zeng Y., Jiang M., Chen R., Zheng P., Yang L., Song Z., Xie D., Chen Y., Yuan Y. (2024) Hsp90aa1/JUN/Ccl2 regulatory axis mediates migration and differentiation of NSPCs, promoting the onset and progression of early post-ischemic stroke epilepsy. Neurobiol. Dis., 200, 106635. CrossRef Scholar google search
Gu C., Wang F., Zhang Y.-T., Wei S.-Z., Liu J.-Y., Sun H.-Y., Wang G.-H., Liu C.-F. (2021) Microglial MT1 activation inhibits LPS-induced neuroinflammation via regulation of metabolic reprogramming. Aging Cell, 20(6), e13375. CrossRef Scholar google search
Ying Z., Najm I., Nemes A., Pinheiro-Martins A.P., Alexopoulos A., Gonzalez-Martinez J., Bingaman W. (2014) Growth-associated protein 43 and progressive epilepsy in cortical dysplasia. Ann. Clin. Transl. Neurol., 1(7), 453–461. CrossRef Scholar google search
Xiao L., Chen W., Guo W., Li H., Chen R., Chen Q. (2025) Exploring the mechanism of action of Phyllanthus emblica in the treatment of epilepsy based on network pharmacology and molecular docking. Medicine (Baltimore), 104(7), e41414. CrossRef Scholar google search
Fan B., Gu J.-Q., Yan R., Zhang H., Feng J., Ikuyama S. (2013) High glucose, insulin and free fatty acid concentrations synergistically enhance perilipin 3 expression and lipid accumulation in macrophages. Metabolism, 62(8), 1168–1179. CrossRef Scholar google search
Wesseling H., Rahmoune H., Tricklebank M., Guest P.C., Bahn S. (2015) A targeted multiplexed proteomic investigation identifies ketamine-induced changes in immune markers in rat serum and expression changes in protein kinases/phosphatases in rat brain. J. Proteome Res., 14(1), 411–421. CrossRef Scholar google search
Tavakkoli A., Abnous K., Vahdati Hassani F., Hosseinzadeh H., Birner-Gruenberger R., Mehri S. (2020) Alteration of protein profile in cerebral cortex of rats exposed to bisphenol A: a proteomics study. Neurotoxicology, 78, 1–10. CrossRef Scholar google search
Wang T., Jia L., Lv B., Liu B., Wang W., Wang F., Yang G., Bu X., Yao L., Zhang B. (2011) Human Ermin (hErmin), a new oligodendrocyte-specific cytoskeletal protein related to epileptic seizure. Brain Res., 1367, 77–84. CrossRef Scholar google search
