Chronic pain in the elderly: Exploring cellular and molecular mechanisms and therapeutic perspectives.

Chronic pain is a debilitating condition frequently observed in the elderly, involving numerous pathological mechanisms within the nervous system. Diminished local blood flow, nerve degeneration, variations in fiber composition, alterations in ion channels and receptors, accompanied by the sustained activation of immune cells and release of pro-inflammatory cytokines, lead to overactivation of the peripheral nervous system. In the central nervous system, chronic pain is strongly associated with the activation of glial cells, which results in central sensitization and increased pain perception. Moreover, age-related alterations in neural plasticity and disruptions in pain inhibitory pathways can exacerbate chronic pain in older adults. Finally, the environmental influences on the development of chronic pain in the elderly must be considered. An understanding of these mechanisms is essential for developing novel treatments for chronic pain, which can significantly improve the quality of life for this vulnerable population.

Chlamydia Trachomatis Prevalence in Asymptomatic Women in Madrid: Study Findings and Their Association with Risk Factors and Mental Health.

BACKGROUND: Chlamydia trachomatis (CT) is a sexually transmitted infection that requires early detection to prevent complications. This study aimed to evaluate the prevalence of CT among asymptomatic women in Spain and investigate the relationship between CT and risk factors associated with sexual practices, as well as factors such as stress and depression. RESULTS: We found that 3.8% of asymptomatic women tested positive for CT. Our findings suggested that having more than five sexual partners increases the risk of sexually transmitted infections (STIs) by 3.87 times when compared with having fewer partners (p = 0.005, OR: 3.87, 95% CI 1.24-11.65). Additionally, 4.5% of participants admitted to using drugs. We found that there was a slightly higher proportion of anxiety and depression among women who tested positive for CT. CONCLUSIONS: We aimed to establish a basis for the implementation of screening in asymptomatic women. Early identification and preventive measures are crucial in minimizing the long-term complications and transmission of the disease. Sexual behavior must be recognized as a risk factor, and women's psychological well-being should be given top priority as a vital aspect of their sexual health.

Enkephalins and Pain Modulation: Mechanisms of Action and Therapeutic Perspectives.

Enkephalins, a subclass of endogenous opioid peptides, play a pivotal role in pain modulation. Enkephalins primarily exert their effects through opioid receptors located widely throughout both the central and peripheral nervous systems. This review will explore the mechanisms by which enkephalins produce analgesia, emotional regulation, neuroprotection, and other physiological effects. Furthermore, this review will analyze the involvement of enkephalins in the modulation of different pathologies characterized by severe pain. Understanding the complex role of enkephalins in pain processing provides valuable insight into potential therapeutic strategies for managing pain disorders.

SARS-CoV-2 E protein interacts with BRD2 and BRD4 SEED domains and alters transcription in a different way than BET inhibition.

Bromodomain and extra-terminal (BET) proteins are relevant chromatin adaptors involved in the transcriptional control of thousands of genes. Two tandem N-terminal bromodomains are essential for chromatin attachment through acetyl-histone recognition. Recently, the BET proteins members BRD2 and BRD4 were found to interact with the SARS-CoV-2 envelope (E) protein, raising the question of whether the interaction constitutes a virus hijacking mechanism for transcription alteration in the host cell. To shed light on this question, we have compared the transcriptome of cells overexpressing E with that of cells treated with the BET inhibitor JQ1. Notably, E overexpression leads to a strong upregulation of natural immunity- and interferon response-related genes. However, BET inhibition results in the downregulation of most of these genes, indicating that these two conditions, far from causing a significant overlap of the altered transcriptomes, course with quite different outputs. Concerning the interaction of E protein with BET members, and differing from previous reports indicating that it occurs through BET bromodomains, we find that it relies on SEED and SEED-like domains, BET regions rich in Ser, Asp, and Glu residues. By taking advantage of this specific interaction, we have been able to direct selective degradation of E protein through a PROTAC system involving a dTAG-SEED fusion, highlighting the possible therapeutic use of this peptide for targeted degradation of a viral essential protein.

Structural diversification of vitamin D using microbial biotransformations.

Vitamin D deficiencies are linked to multiple human diseases. Optimizing its synthesis, physicochemical properties, and delivery systems while minimizing side effects is of clinical relevance and is of great medical and industrial interest. Biotechnological techniques may render new modified forms of vitamin D that may exhibit improved absorption, stability, or targeted physiological effects. Novel modified vitamin D derivatives hold promise for developing future therapeutic approaches and addressing specific health concerns related to vitamin D deficiency or impaired metabolism, such as avoiding hypercalcemic effects. Identifying and engineering key enzymes and biosynthetic pathways involved, as well as developing efficient cultures, are therefore of outmost importance and subject of intense research. Moreover, we elaborate on the critical role that microbial bioconversions might play in the a la carte design, synthesis, and production of novel, more efficient, and safer forms of vitamin D and its analogs. In summary, the novelty of this work resides in the detailed description of the physiological, medical, biochemical, and epidemiological aspects of vitamin D supplementation and the steps towards the enhanced and simplified industrial production of this family of bioactives relying on microbial enzymes. KEY POINTS: • Liver or kidney pathologies may hamper vitamin D biosynthesis • Actinomycetes are able to carry out 1α- or 25-hydroxylation on vitamin D precursors.

Indicators of Dietary Behavior and Physical Activity Change Associated with Metabolic Control of Obesity, Hypertension, and Type 2 Diabetes Mellitus in Mexican Adults: National Nutrition and Health Survey in Mexico, 2016.

Introduction: Obesity (OB), type 2 diabetes mellitus (T2D), and hypertension (HTN) are health issues in Mexico linked to unhealthy behaviors. This study investigates the relationship between behavior change indicators and metabolic control in Mexican adults with OB, T2D, and HTN. Methods: We used data from the 2016 National Health and Nutrition Survey Midway (ENSANUT MC-2016), representing ∼59.5 million Mexican adults aged 20-59 with these conditions. We assessed behavior change indicators, including stages of change, self-efficacy, and perceptions of benefits and barriers. In addition, we conducted descriptive analyses and used statistical tests, such as Pearson's chi-squared test and logistic regression models, adjusted for multiple variables. Results: We found that adults in the action and maintenance stages of physical activity (PA) were four times more likely to have adequate HTN control than those in the precontemplation stage. Self-efficacy for PA was related to better control in T2D and HTN. Self-efficacy for reducing the consumption of sugary beverages was positively associated with control in OB and T2D. No significant association was observed with self-efficacy for consuming fruits and vegetables. Conclusion: Behavior-change indicators are significantly linked to metabolic control in adults with HTN. These results support the importance of these indicators in managing chronic diseases such as HTN and their potential use in public health strategies.

Neoadjuvant chemotherapy with dose-dense MVAC in muscle-invasive bladder cancer: a tertiary center experience

Purpose Neoadjuvant chemotherapy in muscle-invasive bladder cancer (MIBC) patients has proven beneficial in overall survival. However, the optimal regimen is still a matter of debate. Materials and method In this retrospective analysis, we evaluate the results obtained in 42 patients treated in our center with 4 cycles of neoadjuvant dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (dd-MVAC) followed by radical cystectomy from August 2015 to October 2020. All patients had cT2 or higher non-metastatic MIBC. Clinical and pathological outcomes are reported. Results Of the 42 patients, 90.5% were men (n = 38) and the mean age was 65 years. All of them had ECOG 0–1 at diagnosis and most tumors had an initial clinical stage T2N0 (76%). Thirty-six patients (85.7%) completed 4 cycles of neoadjuvant treatment, and 21.4% required a dose reduction. The most frequent adverse event (AE) was grade 1–2 asthenia (81%), while neutropenia was the most frequent grade 3 or higher AE (38%). Complete pathological response (ypT0, ypN0) was achieved in 50% of patients (n = 21), and down-staging was observed in 57.1% (n = 24). Only one patient presented radiological progressive disease during neoadjuvant treatment (2.4%), and after a mean follow-up time of 31.5 months, 33.3% of patients experienced disease recurrence. Conclusions Neoadjuvant chemotherapy with 4 cycles of dd-MVAC is an effective regimen with high rates of pathological complete responses and down-staging along with an acceptable toxicity profile. DD-MVAC should be considered as an alternative to cisplatin and gemcitabine in patients with good clinical performance status (AU)

Topological regulation of the estrogen transcriptional response by ZATT-mediated inhibition of TOP2B activity.

Human type-II topoisomerases, TOP2A and TOP2B, remove transcription associated DNA supercoiling, thereby affecting gene-expression programs, and have recently been associated with 3D genome architecture. Here, we study the regulatory roles of TOP2 paralogs in response to estrogen, which triggers an acute transcriptional induction that involves rewiring of genome organization. We find that, whereas TOP2A facilitates transcription, as expected for a topoisomerase, TOP2B limits the estrogen response. Consistent with this, TOP2B activity is locally downregulated upon estrogen treatment to favor the establishment and stabilization of regulatory chromatin contacts, likely through an accumulation of DNA supercoiling. We show that estrogen-mediated inhibition of TOP2B requires estrogen receptor α (ERα), a non-catalytic function of TOP2A, and the action of the atypical SUMO-ligase ZATT. This mechanism of topological transcriptional-control, which may be shared by additional gene-expression circuits, highlights the relevance of DNA topoisomerases as central actors of genome dynamics.

Factors Associated with SARS-CoV-2 Infection in Fully Vaccinated Nursing Home Residents and Workers.

Persons living or working in nursing homes faced a higher risk of SARS-CoV-2 infections during the pandemic, resulting in heightened morbidity and mortality among older adults despite robust vaccination efforts. This prospective study evaluated the humoral and cellular immunity in fully vaccinated residents and workers from two nursing homes in Madrid, Spain, from 2020 to 2021. Measurements of IgG levels were conducted in August 2020 (pre-vaccination) and June and September 2021 (post-vaccination), alongside assessments of neutralizing antibodies and cellular responses in September 2021 among the most vulnerable individuals. Follow-up extended until February 2022 to identify risk factors for SARS-CoV-2 infection or mortality, involving 267 residents (mean age 87.6 years, 81.3% women) and 302 workers (mean age 50.7 years, 82.1% women). Residents exhibited a significantly higher likelihood of experiencing COVID-19 before June 2021 compared with nursing staff (OR [95% CI], 7.2 [3.0 to 17.2], p < 0.01). Participants with a history of previous COVID-19 infection showed more significant increases in IgG levels in August 2020, June 2021 and September 2021, alongside an increased proportion of neutralizing antibodies in the most vulnerable individuals. However, IgG decay remained the same between June and September 2021 based on the previous COVID-19 status. During the Omicron variant wave, residents and staff showed a similar rate of SARS-CoV-2 infection. Notably, preceding clinical or immunological factors before receiving three vaccination doses did not demonstrate associations with COVID-19 infection or overall mortality in our participant cohort.

Membrane computing simulation of sexually transmitted bacterial infections in hotspots of individuals with various risk behaviors.

The epidemiology of sexually transmitted infections (STIs) is complex due to the coexistence of various pathogens, the variety of transmission modes derived from sexual orientations and behaviors at different ages and genders, and sexual contact hotspots resulting in network transmission. There is also a growing proportion of recreational drug users engaged in high-risk sexual activities, as well as pharmacological self-protection routines fostering non-condom practices. The frequency of asymptomatic patients makes it difficult to develop a comprehensive approach to STI epidemiology. Modeling approaches are required to deal with such complexity. Membrane computing is a natural computing methodology for the virtual reproduction of epidemics under the influence of deterministic and stochastic events with an unprecedented level of granularity. The application of the LOIMOS program to STI epidemiology illustrates the possibility of using it to shape appropriate interventions. Under the conditions of our basic landscape, including sexual hotspots of individuals with various risk behaviors, an increase in condom use reduces STIs in a larger proportion of heterosexuals than in same-gender sexual contacts and is much more efficient for reducing Neisseria gonorrhoeae than Chlamydia and lymphogranuloma venereum infections. Amelioration from diagnostic STI screening could be instrumental in reducing N. gonorrhoeae infections, particularly in men having sex with men (MSM), and Chlamydia trachomatis infections in the heterosexual population; however, screening was less effective in decreasing lymphogranuloma venereum infections in MSM. The influence of STI epidemiology of sexual contacts between different age groups (<35 and ≥35 years) and in bisexual populations was also submitted for simulation.IMPORTANCEThe epidemiology of sexually transmitted infections (STIs) is complex and significantly influences sexual and reproductive health worldwide. Gender, age, sexual orientation, sexual behavior (including recreational drug use and physical and pharmacological protection practices), the structure of sexual contact networks, and the limited application or efficiency of diagnostic screening procedures create variable landscapes in different countries. Modeling techniques are required to deal with such complexity. We propose the use of a simulation technology based on membrane computing, mimicking in silico STI epidemics under various local conditions with an unprecedented level of detail. This approach allows us to evaluate the relative weight of the various epidemic drivers in various populations at risk and the possible outcomes of interventions in particular epidemiological landscapes.

Rapid expansion of lymphogranuloma venereum infections with fast diversification and spread of Chlamydia trachomatis L genovariants.

IMPORTANCE: Numerous international organizations, including the World Health Organization, have been drawing attention to the global increase in sexually transmitted infections. Twenty years ago, lymphogranuloma venereum (LGV) was mainly considered a tropical disease; in recent decades, however, LGV has been increasingly present in high-income countries. This increase has been linked to men who have sex with men who participate in highly interconnected sexual networks, leading to a rapid spread of LGV. This study focuses on the spread of LGV, presenting the largest time series of LGV prevalence in Spain, which includes more than a thousand diagnosed cases in one large city. The number of LGV cases diagnosed was analyzed over time, and a selection of strains was subjected to molecular genotyping. The results indicate that the LGV epidemic is gradually evolving toward an increasingly complex diversification due to the selection of successful genovariants that have emerged by mutation and recombination events, suggesting that we are moving toward an unpredictable scenario.

Neoadjuvant chemotherapy with dose-dense MVAC in muscle-invasive bladder cancer: a tertiary center experience.

PURPOSE: Neoadjuvant chemotherapy in muscle-invasive bladder cancer (MIBC) patients has proven beneficial in overall survival. However, the optimal regimen is still a matter of debate. MATERIALS AND METHODS: In this retrospective analysis, we evaluate the results obtained in 42 patients treated in our center with 4 cycles of neoadjuvant dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (dd-MVAC) followed by radical cystectomy from August 2015 to October 2020. All patients had cT2 or higher non-metastatic MIBC. Clinical and pathological outcomes are reported. RESULTS: Of the 42 patients, 90.5% were men (n = 38) and the mean age was 65 years. All of them had ECOG 0-1 at diagnosis and most tumors had an initial clinical stage T2N0 (76%). Thirty-six patients (85.7%) completed 4 cycles of neoadjuvant treatment, and 21.4% required a dose reduction. The most frequent adverse event (AE) was grade 1-2 asthenia (81%), while neutropenia was the most frequent grade 3 or higher AE (38%). Complete pathological response (ypT0, ypN0) was achieved in 50% of patients (n = 21), and down-staging was observed in 57.1% (n = 24). Only one patient presented radiological progressive disease during neoadjuvant treatment (2.4%), and after a mean follow-up time of 31.5 months, 33.3% of patients experienced disease recurrence. CONCLUSIONS: Neoadjuvant chemotherapy with 4 cycles of dd-MVAC is an effective regimen with high rates of pathological complete responses and down-staging along with an acceptable toxicity profile. DD-MVAC should be considered as an alternative to cisplatin and gemcitabine in patients with good clinical performance status.

Políticas nacionales para el control del VIH y la evolución de la epidemia en México: un análisis de 1990 a 2017.

OBJETIVO: Analizar los cambios en la carga de la enfermedad del VIH de 1990-2017 y la influencia de las políticas y programas implementadas para su prevención y control. Material y métodos. Se elaboró una línea de tiempo de políticas e intervenciones en México; mediante modelos de regresión JoinPoint, se analizó su relación con los cambios ocurridos en las tendencias de la carga de la enfermedad del VIH. RESULTADOS: Los cambios en la carga de enfermedad se relacionan con la universalización del acceso a los medicamentos antirretrovirales (ARV), programas de atención integral y el combate al estigma y la discriminación. En el periodo analizado se observa descenso de la mortalidad relacionado con el acceso universal y gratuito a los ARV. La magnitud de los cambios tiende a ser mayor en los hombres que en las mujeres. CONCLUSIONES: Las políticas y programas implementados para tratar a las personas con VIH/Sida en México se integraron en estrategias cada vez más cohesionadas y eficaces.

Design and implementation of AMBAR: an innovative evidence-based training program for childbirth and newborn care.

OBJECTIVE: To present the development of a training model called AMBAR (Atención a la mujer embarazada y al recién nacido [Care for pregnant women and newborns]), which was designed to improve the quality of attention of health personnel responsible for obstetric care. MATERIALS AND METHODS: AMBAR was designed based on the results of a qualitative study exploring public health providers' needs and experiences. It was implemented in three health networks, and a total of 339 health personnel participated. RESULTS: The educational design of the course was appealing to the trained personnel, and the inclusion of simulations in all modules encouraged interest, participation, as well as the integration of new knowledge and skills into practice. CONCLUSION: AMBAR can promote better practices and increase the quality of birth care. With the proper support and willingness of staff and management, AMBAR can be implemented in all health services, both public and private.

Synthesis and interaction with growth factors of sulfated oligosaccharides containing an anomeric fluorinated tail.

Compounds that mimic the biological properties of glycosaminoglycans (GAGs) and can be more easily prepared than the native GAG oligosaccharides are highly demanded. Here, we present the synthesis of sulfated oligosaccharides displaying a perfluorinated aliphatic tag at the reducing end as GAG mimetics. The preparation of these molecules was greatly facilitated by the presence of the fluorinated tail since the reaction intermediates were isolated by simple fluorous solid-phase extraction. Fluorescence polarization competition assays indicated that the synthesized oligosaccharides interacted with two heparin-binding growth factors, midkine (MK) and FGF-2, showing higher binding affinities than the natural oligosaccharides, and can be therefore considered as useful GAG mimetics. Moreover, NMR experiments showed that the 3D structure of these compounds is similar to that of the native sequences, in terms of sugar ring and glycosidic linkage conformations. Finally, we also demonstrated that these derivatives are able to block the MK-stimulating effect on NIH3T3 cells growth.

[Use of antibiotics, in a pediatric hospital, for respiratory infection and diarrheal disease]. / Uso de antibióticos, en hospital pediátrico, para infección respiratoria y enfermedad diarreica.

Background: The World Health Organization (WHO) reports an increasing unjustified use of antibiotics in the treatment of Acute Respiratory Infections (ARI) and Acute Diarrheal Diseases (ADD) in children under five years of age. This has generated problems such as polypharmacy and the inappropriate use of antibiotics; characterized by incorrect dosage, use in viral infections, prescription inconsistent with clinical guidelines. Objective: To analyze the prescription of antibiotics, their diagnostic-therapeutic congruence, as well as the correct filling of the medical prescription, in a tertiary level hospital in Mexico. Material and methods: Observational, descriptive cross-sectional study. The electronic medical prescriptions made during the period January-December 2017 with a clinical diagnosis of ARI and EDA were analyzed. Results: Of a total of 21,446 boys and girls under five years of age, 10,233 prescriptions were issued for the treatment of ARI and ADD diagnoses. 80% of the prescriptions complied with the items indicated in the electronic file. Conclusions: The prescription of antibiotics showed a prudent use of antibiotics both in the management of acute diarrheal diseases and in the management of acute respiratory diseases. Diagnostic-therapeutic congruence was found in most of the cases in the prescriptions analyzed.

Introducción: la Organización Mundial de Salud (OMS) reporta un creciente uso injustificado de antibióticos en el tratamiento de las infecciones respiratorias agudas (IRA) y las enfermedades diarreicas agudas (EDA) en menores de cinco años de edad. Lo anterior ha generado problemas como la polifarmacia y el uso inapropiado de antibióticos, caracterizado por dosis incorrectas, uso en infecciones virales y prescripción incongruente con las directrices clínicas. Objetivo: analizar la prescripción de antibióticos, su congruencia diagnóstico-terapéutica, así como el correcto llenado de la receta médica, en un hospital de tercer nivel de México. Material y métodos: estudio transversal observacional, descriptivo. Se analizó las recetas médicas electrónicas realizadas durante el periodo enero-diciembre de 2017 con diagnóstico clínico de IRA y EDA. Resultados: de un total de 21,446 niños y niñas menores de cinco años se otorgaron 10, 233 recetas para el tratamiento de los diagnósticos de IRA y EDA. El 80% de las recetas cumplieron con de los rubros indicados en el expediente electrónico. Conclusiones: la prescripción de antibióticos mostró un uso prudente de antibióticos tanto en el manejo de las enferdades diarreicas agudas como en el manejo de las enfermedades respiratorias agudas. Se encontró, en la mayoría de los casos, congruencia diagnóstico-terapéutica en las prescripciones analizadas.

Effectiveness and safety of tildrakizumab for the treatment of psoriasis in real-world settings at 24 weeks: A retrospective, observational, multicentre study by the Spanish Psoriasis Group.

BACKGROUND: Tildrakizumab is a humanized, IgG1/κ antibody that interacts with the p19 subunit of interleukin 23. It is approved for the treatment of moderate-to-severe plaque psoriasis. Real-world evidence on the effectiveness and safety of tildrakizumab is limited. OBJECTIVES: To assess the effectiveness and safety of tildrakizumab at 24 weeks in patients with moderate-to-severe plaque psoriasis in routine clinical practice. METHODS: Retrospective, observational, multicentre study including adult patients with moderate-to-severe plaque psoriasis treated with tildrakizumab under real-life conditions. Patient data were extracted from anonymized electronic medical records. Statistical analysis was performed using SPSS22. RESULTS: A total of 190 patients were included. About 53.9% were men with a mean age of 51.45 (SD 3.9) and a mean BMI of 29.13 (SD 6.21). About 79.8% (132 out of 190) of patients had previously received biological therapy (BT) and 17.3% (33 out of 191) had psoriatic arthritis. Baseline PASI was 10.7 (SD 6.53). Up to 109 patients reached Week 24 and at this point mean baseline PASI decreased to 1.7 (SD 4.8), representing an 88.79% mean PASI reduction. At 6 months, 87.1% and 40.3% of the treated patients achieved PASI ≤3 and ≤1, respectively. At Week 24 mean BSA decreased from 13.2 (SD 10.07) to 1.6 (SD 4.40) and mean DLQI went from 12.5 (SD 7.12) to 1.2 (SD 3.27). Multivariate analysis showed no differences when effectiveness was correlated with gender, obesity, psoriatic arthritis or prior exposure to BT. The rate of adverse events (AE) was 5.9% (11 out of 190), where infections were the most frequent AE (4 out of 11). One patient suffered a haemorrhagic ictus and one patient died due to causes unrelated to the study. CONCLUSION: Tildrakizumab was effective and safe in a large cohort of patients with moderate-to-severe plaque psoriasis treated in a routine clinical setting.

Exome sequencing links the SUMO protease SENP7 with fatal arthrogryposis multiplex congenita, early respiratory failure and neutropenia.

BACKGROUND: SUMOylation involves the attachment of small ubiquitin-like modifier (SUMO) proteins to specific lysine residues on thousands of substrates with target-specific effects on protein function. Sentrin-specific proteases (SENPs) are proteins involved in the maturation and deconjugation of SUMO. Specifically, SENP7 is responsible for processing polySUMO chains on targeted substrates including the heterochromatin protein 1α (HP1α). METHODS: We performed exome sequencing and segregation studies in a family with several infants presenting with an unidentified syndrome. RNA and protein expression studies were performed in fibroblasts available from one subject. RESULTS: We identified a kindred with four affected subjects presenting with a spectrum of findings including congenital arthrogryposis, no achievement of developmental milestones, early respiratory failure, neutropenia and recurrent infections. All died within four months after birth. Exome sequencing identified a homozygous stop gain variant in SENP7 c.1474C>T; p.(Gln492*) as the probable aetiology. The proband's fibroblasts demonstrated decreased mRNA expression. Protein expression studies showed significant protein dysregulation in total cell lysates and in the chromatin fraction. We found that HP1α levels as well as different histones and H3K9me3 were reduced in patient fibroblasts. These results support previous studies showing interaction between SENP7 and HP1α, and suggest loss of SENP7 leads to reduced heterochromatin condensation and subsequent aberrant gene expression. CONCLUSION: Our results suggest a critical role for SENP7 in nervous system development, haematopoiesis and immune function in humans.

MAPK/MAK/MRK overlapping kinase (MOK) controls microglial inflammatory/type-I IFN responses via Brd4 and is involved in ALS.

Amyotrophic lateral sclerosis (ALS) is a fatal and incurable neurodegenerative disease affecting motor neurons and characterized by microglia-mediated neurotoxic inflammation whose underlying mechanisms remain incompletely understood. In this work, we reveal that MAPK/MAK/MRK overlapping kinase (MOK), with an unknown physiological substrate, displays an immune function by controlling inflammatory and type-I interferon (IFN) responses in microglia which are detrimental to primary motor neurons. Moreover, we uncover the epigenetic reader bromodomain-containing protein 4 (Brd4) as an effector protein regulated by MOK, by promoting Ser492-phospho-Brd4 levels. We further demonstrate that MOK regulates Brd4 functions by supporting its binding to cytokine gene promoters, therefore enabling innate immune responses. Remarkably, we show that MOK levels are increased in the ALS spinal cord, particularly in microglial cells, and that administration of a chemical MOK inhibitor to ALS model mice can modulate Ser492-phospho-Brd4 levels, suppress microglial activation, and modify the disease course, indicating a pathophysiological role of MOK kinase in ALS and neuroinflammation.