{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T15:11:33Z","timestamp":1787238693795,"version":"build-2736575974"},"reference-count":59,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T00:00:00Z","timestamp":1763683200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Chronic low-grade systemic inflammation is increasingly recognized as a key mediator linking stress, pain sensitivity, and cognitive decline. Central to this process are the acute-phase reactants interleukin-6 (IL-6) and C-reactive protein (CRP), which serve as biomarkers of systemic inflammation while promoting neuroimmune dysregulation. Emerging evidence implicates the IL-6\u2013CRP axis in the amplification of pain perception, central sensitization, and stress hypersensitivity, ultimately promoting neurodegenerative processes such as those observed in Alzheimer\u2019s disease (AD) and vascular dementia. Monomeric CRP (mCRP), a proinflammatory isoform generated under mechanical or oxidative stress, can trigger histone modifications (e.g., H3 citrullination), activate endothelial and immune cells, and exacerbate inflammatory pain pathways. These mechanisms are further modulated by genetic and epigenetic factors, including IL-6\/CRP\/NR3C1 gene variant expression; promoter methylation; and stress-responsive microRNAs, which intersect with dysregulation of the hypothalamic\u2013pituitary\u2013adrenal (HPA) axis, impairing immune resolution and neurocognitive resilience. Psychosocial stressors, such as the burden of caregiving or perfectionistic cognitive patterns, amplify IL-6 and CRP levels, particularly when pain is present, suggesting a synergistic interaction between emotional distress and somatic inflammation. Specifically, elevated CRP is associated with increased pain sensitivity, lower pain thresholds, and cognitive decline even in subclinical populations, providing a feedforward model in which chronic stress and pain potentiate systemic inflammation, disrupt neuroendocrine feedback, and accelerate neurodegenerative pathology. However, in this model, the potentially critical mechanistic and pathological role of mCRP remains to be discovered. This review addresses the missing elements of these overlapping pathways and discusses the therapeutic potential of targeting IL-6\u2013CRP signaling, stress regulation, and epigenetic modifiers as strategies to ameliorate inflammation-driven cognitive decline and enhance stress resistance in chronic disease contexts. We propose that plasma mCRP or more likely the isoform-aware metric, the mCRP\/CRP ratio, will provide a biologically anchored, potentially more discriminative approach to vascular-neuroimmune risk and capture the propensity for local effector signaling, likely outperforming hs-CRP or IL-6 alone for risk stratification across neurovascular and stress-sensitized pain phenotypes.<\/jats:p>","DOI":"10.3390\/ijms262311279","type":"journal-article","created":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T15:33:06Z","timestamp":1763739186000},"page":"11279","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Monomeric [CRP] and CRP-Controlled Stress and Pain Hypersensitization as Novel Predictors of Cognitive Disturbance and AD in Chronic Inflammatory Disease"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3767-4861","authenticated-orcid":false,"given":"Mark","family":"Slevin","sequence":"first","affiliation":[{"name":"Centre for Advanced Medical and Pharmaceutical Research, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of T\u00e2rgu Mure\u0219, 38th Gh. Marinescu Street, 540139 T\u00e2rgu Mure\u015f, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9704-869X","authenticated-orcid":false,"given":"Amelia","family":"Tero-Vescan","sequence":"additional","affiliation":[{"name":"Department of Medical Chemistry and Biochemistry, Faculty of Medicine in English, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of T\u00e2rgu Mure\u0219, 38th Gh. Marinescu Street, 540139 T\u00e2rgu Mure\u015f, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Cooper, J., Pastorello, Y., and Slevin, M. (2023). A Meta-Analysis Investigating the Relationship between Inflammation in Autoimmune Disease, Elevated CRP, and the Risk of Dementia. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1087571"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e13501","DOI":"10.1111\/acel.13501","article-title":"Monomeric C-reactive Protein via Endothelial CD31 for Neurovascular Inflammation in an ApoE Genotype-dependent Pattern: A Risk Factor for Alzheimer\u2019s Disease?","volume":"20","author":"Zhang","year":"2021","journal-title":"Aging Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1093\/gerona\/gls187","article-title":"The Role of Peripheral Inflammatory Markers in Dementia and Alzheimer\u2019s Disease: A Meta-Analysis","volume":"68","author":"Koyama","year":"2013","journal-title":"J. Gerontol. Ser. A Biol. Sci. Med. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.jocn.2022.11.016","article-title":"Peripheral High Levels of CRP Predict Progression from Normal Cognition to Dementia: A Systematic Review and Meta-Analysis","volume":"107","author":"Long","year":"2023","journal-title":"J. Clin. Neurosci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1822","DOI":"10.1158\/1078-0432.CCR-23-3709","article-title":"Systemic Biological Mechanisms of Neurocognitive Dysfunction in Long-Term Survivors of Childhood Hodgkin Lymphoma","volume":"30","author":"Williams","year":"2024","journal-title":"Clin. Cancer Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"317","DOI":"10.62641\/aep.v52i3.1657","article-title":"Correlation between the Degree of Inflammation and Stress Indicators and Concurrent Cognitive Impairment in Patients with Severe Craniocerebral Injury","volume":"52","author":"Yuan","year":"2024","journal-title":"Actas Esp. Psiquiatr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1016\/j.jad.2020.10.045","article-title":"Association of CRP Genetic Variation with Symptomatology, Cognitive Function, and Circulating Proinflammatory Markers in Civilian Women with PTSD","volume":"279","author":"Otsuka","year":"2021","journal-title":"J. Affect. Disord."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Thomas, A., Guo, J., Reyes-Dumeyer, D., Sanchez, D., Scarmeas, N., Manly, J.J., Brickman, A.M., Lantigua, R.A., Mayeux, R., and Gu, Y. (2025). Inflammatory Biomarkers Profiles and Cognition among Older Adults. Sci. Rep., 15.","DOI":"10.1038\/s41598-025-86309-z"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Fujita, C., Sakurai, Y., Yasuda, Y., Homma, R., Huang, C.-L., and Fujita, M. (2022). mCRP as a Biomarker of Adult-Onset Still\u2019s Disease: Quantification of mCRP by ELISA. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.938173"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Williams, R.D., Moran, J.A., Fryer, A.A., Littlejohn, J.R., Williams, H.M., Greenhough, T.J., and Shrive, A.K. (2020). Monomeric C-Reactive Protein in Serum with Markedly Elevated CRP Levels Shares Common Calcium-Dependent Ligand Binding Properties with an in Vitro Dissociated Form of C-Reactive Protein. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.00115"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"7393","DOI":"10.1038\/s41380-021-01188-w","article-title":"Association of inflammation with depression and anxiety: Evidence for symptom-specificity and potential causality from UK Biobank and NESDA cohorts","volume":"26","author":"Milaneschi","year":"2021","journal-title":"Mol. Psychiatry"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.neuron.2020.06.002","article-title":"The Bidirectional Relationship of Depression and Inflammation: Double Trouble","volume":"107","author":"Beurel","year":"2020","journal-title":"Neuron"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.biopsych.2015.05.014","article-title":"Sleep Disturbance, Sleep Duration, and Inflammation: A Systematic Review and Meta-Analysis of Cohort Studies and Experimental Sleep Deprivation","volume":"80","author":"Irwin","year":"2016","journal-title":"Biol. Psychiatry"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Beiner, E., Brenner Miguel, S., Friederich, H.-C., and Tesarz, J. (2023). PerPAIN Consortium Elevated High Sensitive C-Reactive Protein in Fibromyalgia. Front. Psychiatry, 14.","DOI":"10.3389\/fpsyt.2023.1237518"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1093\/ibd\/izac089","article-title":"Multimodal Brain MRI of Deep Gray Matter Changes Associated with Inflammatory Bowel Disease","volume":"29","author":"Goodyear","year":"2023","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1097\/NNR.0000000000000013","article-title":"The Association of Pain with Protein Inflammatory Biomarkers: A Review of the Literature","volume":"63","author":"DeVon","year":"2014","journal-title":"Nurs. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/j.bbi.2005.11.002","article-title":"Hostility and Pain Are Related to Inflammation in Older Adults","volume":"20","author":"Graham","year":"2006","journal-title":"Brain Behav. Immun."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2140","DOI":"10.1016\/j.spinee.2018.06.349","article-title":"The Association between Pro-Inflammatory Biomarkers and Nonspecific Low Back Pain: A Systematic Review","volume":"18","author":"Jongbloed","year":"2018","journal-title":"Spine J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1037\/a0025536","article-title":"Chronic Stress, Daily Stressors, and Circulating Inflammatory Markers","volume":"31","author":"Gouin","year":"2012","journal-title":"Health Psychol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e002945","DOI":"10.1136\/rmdopen-2022-002945","article-title":"Associations between Markers of Inflammation and Altered Pain Perception Mechanisms in People with Knee Osteoarthritis: A Systematic Review","volume":"9","author":"Dainese","year":"2023","journal-title":"RMD Open"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Shakouri, S.K., Dolatkhah, N., Omidbakhsh, S., Pishgahi, A., and Hashemian, M. (2020). Serum Inflammatory and Oxidative Stress Biomarkers Levels Are Associated with Pain Intensity, Pressure Pain Threshold and Quality of Life in Myofascial Pain Syndrome. BMC Res. Notes, 13.","DOI":"10.1186\/s13104-020-05352-3"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1097\/j.pain.0000000000000912","article-title":"C-Reactive Protein and Cold-Pressor Tolerance in the General Population: The Troms\u00f8 Study","volume":"158","author":"Schistad","year":"2017","journal-title":"Pain"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"100431","DOI":"10.1016\/j.bbih.2022.100431","article-title":"Individuals with Both Higher Recent Negative Affect and Physical Pain Have Higher Levels of C-Reactive Protein","volume":"21","author":"DeMeo","year":"2022","journal-title":"Brain Behav. Immun. Health"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"100176","DOI":"10.1016\/j.bbih.2020.100176","article-title":"IL-6 and hsCRP in Somatic Symptom Disorders and Related Disorders","volume":"9","author":"Bakker","year":"2020","journal-title":"Brain Behav. Immun. Health"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"100211","DOI":"10.1016\/j.bbih.2021.100211","article-title":"Perfectionistic Cognitions, Interleukin-6, and C-Reactive Protein: A Test of the Perfectionism Diathesis Stress Model","volume":"13","author":"Molnar","year":"2021","journal-title":"Brain Behav. Immun. Health"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.bbi.2019.01.002","article-title":"Circulating Interleukin-6 Concentration Covaries Inversely with Self-Reported Sleep Duration as a Function of Polymorphic Variation in the Glucocorticoid Receptor","volume":"78","author":"Walsh","year":"2019","journal-title":"Brain Behav. Immun."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"107272","DOI":"10.1016\/j.psyneuen.2024.107272","article-title":"Cortisol and C-Reactive Protein (CRP) Regulation in Severe Mental Disorders","volume":"172","author":"Inova","year":"2025","journal-title":"Psychoneuroendocrinology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1161\/CIRCRESAHA.124.324248","article-title":"Shear-Sensing by C-Reactive Protein: Linking Aortic Stenosis and Inflammation","volume":"135","author":"Zeller","year":"2024","journal-title":"Circ. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2239","DOI":"10.1161\/ATVBAHA.108.174359","article-title":"C-Reactive Protein Isoforms Differ in Their Effects on Thrombus Growth","volume":"28","author":"Molins","year":"2008","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1172\/JCI2629","article-title":"The Effect of Novel Polymorphisms in the Interleukin-6 (IL-6) Gene on IL-6 Transcription and Plasma IL-6 Levels, and an Association with Systemic-Onset Juvenile Chronic Arthritis","volume":"102","author":"Fishman","year":"1998","journal-title":"J. Clin. Investig."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1210\/rp.59.1.333","article-title":"Polymorphisms in the Glucocorticoid Receptor Gene and Their Associations with Metabolic Parameters and Body Composition","volume":"59","year":"2004","journal-title":"Recent Prog. Horm. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.bbi.2020.12.033","article-title":"Stress Impairs Response to Antidepressants via HPA Axis and Immune System Activation","volume":"93","author":"Menke","year":"2021","journal-title":"Brain Behav. Immun."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"14716","DOI":"10.1073\/pnas.0902971106","article-title":"Low Early-Life Social Class Leaves a Biological Residue Manifested by Decreased Glucocorticoid and Increased Proinflammatory Signaling","volume":"106","author":"Miller","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Pereira-da-Silva, T., Napole\u00e3o, P., Costa, M.C., Gabriel, A.F., Selas, M., Silva, F., Enguita, F.J., Cruz Ferreira, R., and Mota Carmo, M. (2021). Association between miR-146a and Tumor Necrosis Factor Alpha (TNF-\u03b1) in Stable Coronary Artery Disease. Medicina, 57.","DOI":"10.3390\/medicina57060575"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Karasu, E., Halbgebauer, R., Sch\u00fctte, L., Greven, J., Bl\u00e4sius, F.M., Zeller, J., Winninger, O., Braig, D., Messerer, D.A.C., and Berger, B. (2025). A Conformational Change of C-Reactive Protein Drives Neutrophil Extracellular Trap Formation in Inflammation. BMC Biol., 23.","DOI":"10.1186\/s12915-024-02093-8"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.maturitas.2018.10.014","article-title":"Anxiety and Risk of Dementia: Systematic Review and Meta-Analysis of Prospective Cohort Studies","volume":"119","author":"Lipnicki","year":"2019","journal-title":"Maturitas"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/S2215-0366(17)30293-6","article-title":"The Blood\u2013Brain Barrier in Psychosis","volume":"5","author":"Pollak","year":"2018","journal-title":"Lancet Psychiatry"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3698","DOI":"10.1038\/s41380-023-02255-0","article-title":"Brain Microvascular Endothelial Cells and Blood-Brain Barrier Dysfunction in Psychotic Disorders","volume":"28","author":"Lizano","year":"2023","journal-title":"Mol. Psychiatry"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Yamaguchi, T., Shimizu, K., Kokubu, Y., Nishijima, M., Takeda, S., Ogura, H., and Kawabata, K. (2019). Effect of Heat Stress on Blood-Brain Barrier Integrity in iPS Cell-Derived Microvascular Endothelial Cell Models. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0222113"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1111\/1440-1681.12758","article-title":"C-reactive Protein and Ageing","volume":"44","author":"Tang","year":"2017","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"You, Y.-K., Huang, X.-R., Chen, H.-Y., Lyu, X.-F., Liu, H.-F., and Lan, H.Y. (2016). C-Reactive Protein Promotes Diabetic Kidney Disease in Db\/Db Mice via the CD32b-Smad3-mTOR Signaling Pathway. Sci. Rep., 6.","DOI":"10.1038\/srep26740"},{"key":"ref_42","first-page":"930","article-title":"Serum Claudin-5 levels facilitate the early prediction of severe acute pancreatitis: A prospective observational study","volume":"36","author":"Chen","year":"2024","journal-title":"Zhonghua Wei Zhong Bing Ji Jiu Yi Xue"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Bell, T.R., Franz, C.E., Thomas, K.R., Williams, M.E., Eyler, L.T., Lerman, I., Fennema-Notestine, C., Puckett, O.K., Dorros, S.M., and Panizzon, M.S. (2024). Elevated C-Reactive Protein in Older Men with Chronic Pain: Association with Plasma Amyloid Levels and Hippocampal Volume. J. Gerontol. Ser. A Biol. Sci. Med. Sci., 79.","DOI":"10.1093\/gerona\/glae206"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"100781","DOI":"10.1016\/j.bbih.2024.100781","article-title":"Mapping Pathways to Neuronal Atrophy in Healthy, Mid-Aged Adults: From Chronic Stress to Systemic Inflammation to Neurodegeneration?","volume":"38","author":"Schaefer","year":"2024","journal-title":"Brain Behav. Immun. Health"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1038\/s41392-024-01845-w","article-title":"Pathology of Pain and Its Implications for Therapeutic Interventions","volume":"9","author":"Cao","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1093\/infdis\/jiu224","article-title":"Influenza-like Illness, the Time to Seek Healthcare, and Influenza Antiviral Receipt During the 2010\u20132011 Influenza Season\u2014United States","volume":"210","author":"Biggerstaff","year":"2014","journal-title":"J. Infect. Dis."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1346","DOI":"10.1111\/pme.12460","article-title":"Changes in Clinical Pain in Fibromyalgia Patients Correlate with Changes in Brain Activation in the Cingulate Cortex in a Response Inhibition Task","volume":"15","author":"Kairys","year":"2014","journal-title":"Pain Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1111\/j.1601-0825.2008.01458.x","article-title":"Genetic Contributions to Pain: A Review of Findings in Humans","volume":"14","author":"Fillingim","year":"2008","journal-title":"Oral Dis."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2590","DOI":"10.1016\/j.bmcl.2008.03.040","article-title":"Microarray-Based Label-Free Detection of RNA Using Bispyrene-Modified 2\u2032-O-Methyl Oligoribonucleotide as Capture and Detection Probe","volume":"18","author":"Sakamoto","year":"2008","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Ayub, S., Bachu, A.K., Jain, L., Parnia, S., Bhivandkar, S., Ahmed, R., Kaur, J., Karlapati, S., Prasad, S., and Kochhar, H. (2024). Non-Opioid Psychiatric Medications for Chronic Pain: Systematic Review and Meta-Analysis. Front. Pain Res., 5.","DOI":"10.3389\/fpain.2024.1398442"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Camon, A.M., Alonso, R., Mu\u00f1oz, F.J., Cardozo, C., Bernal-Maurandi, J., Albiach, L., Ag\u00fcero, D., Marcos, M.A., Ambrosioni, J., and Bodro, M. (2022). C-Reactive Protein Cut-off for Early Tocilizumab and Dexamethasone Prescription in Hospitalized Patients with COVID-19. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-08882-x"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e16236","DOI":"10.15252\/emmm.202216236","article-title":"A Novel Phosphocholine-mimetic Inhibits a Pro-inflammatory Conformational Change in C-reactive Protein","volume":"15","author":"Zeller","year":"2023","journal-title":"EMBO Mol. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e005379","DOI":"10.1136\/rmdopen-2024-005379","article-title":"Monomeric C-Reactive Protein as a Therapeutic Target in Inflammatory Diseases","volume":"11","author":"Fujita","year":"2025","journal-title":"RMD Open"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1002\/ejsc.12038","article-title":"A Novel Periodized High-repetition Giant-set Resistance and High-intensity Interval Training Effects on the Metabolic and Pro-inflammatory Parameters in Long-and Short-term Overweight Men","volume":"24","author":"Nikseresht","year":"2024","journal-title":"Eur. J. Sport Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"109952","DOI":"10.1016\/j.neuropharm.2024.109952","article-title":"Glucagon-like Peptide-1 Class Drugs Show Clear Protective Effects in Parkinson\u2019s and Alzheimer\u2019s Disease Clinical Trials: A Revolution in the Making?","volume":"253","year":"2024","journal-title":"Neuropharmacology"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"3145","DOI":"10.2147\/JPR.S320863","article-title":"Understanding the Psychological, Physiological, and Genetic Factors Affecting Precision Pain Medicine: A Narrative Review","volume":"14","author":"Chadwick","year":"2021","journal-title":"J. Pain Res."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Roveta, F., Bonino, L., Piella, E.M., Rainero, I., and Rubino, E. (2024). Neuroinflammatory Biomarkers in Alzheimer\u2019s Disease: From Pathophysiology to Clinical Implications. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms252211941"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Delic, S., Miletic Drakulic, S., Stepovic, M., Milosavljevic, J., Kovacevic Dimitrijevic, M., Jovanovic, K., Marinkovic, I., Tepavcevic, M., Janicijevic, N., and Mitrovic, A. (2025). The Connection Between Oxidative Stress, Mitochondrial Dysfunction, Iron Metabolism and Microglia in Multiple Sclerosis: A Narrative Review. NeuroSci, 6.","DOI":"10.3390\/neurosci6010023"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"7115","DOI":"10.2147\/JIR.S485050","article-title":"Circulating Levels of the Proinflammatory Monomeric Isoform of C-Reactive Protein (mCRP) Correlate with Intra-Tumoral mCRP Abundance in Stage II\u2013III Colon Cancer Patients","volume":"18","author":"Fuglestad","year":"2025","journal-title":"J. Inflamm. Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/23\/11279\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T05:26:19Z","timestamp":1764048379000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/23\/11279"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,21]]},"references-count":59,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["ijms262311279"],"URL":"https:\/\/doi.org\/10.3390\/ijms262311279","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,21]]}}}