Neuroinflammatory disorders of the central nervous system associated with monkeypox virus: a systematic review and call to action

BMC Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: Feb. 12, 2025

Monkeypox virus (MPXV) has emerged as a significant global health concern with outbreaks worldwide. While MPXV is primarily known for its dermatological and systemic manifestations, it can also cause central nervous system (CNS) complications. This systematic review describes the demographic, clinical, diagnostic, therapeutic characteristics of MPXV-associated CNS neuroinflammatory disorders. We systematically reviewed literature to identify cases Data on demographics, neurological diagnostic methods, treatment strategies, outcomes were extracted analyzed. Eighteen disorders identified. The mean age patients was 27.8 years (range: 28 days 43 years), male predominance (66.7%). Diagnosis included most common diagnoses acute disseminated encephalomyelitis in nine (50.0%), encephalitis/meningoencephalitis seven (38.9%, isolated transverse myelitis one case (5.6%), encephalitis (5.6%). latency between onset symptoms involvement averaged 6.2 days. detection confirmed 13 18 (72.2%) cases, using quantitative real-time polymerase chain reaction from various biological specimens. Among 12 documented treatment, commonly administered therapies tecovirimat (58.3%) intravenous methyl-prednisolone Outcomes reported 17 complete recovery 29.4%, partial 41.2%, death 29.4% patients. are rare but findings underscore need clinical vigilance, advanced approaches, targeted strategies. Further research essential elucidate mechanisms underlying neurovirulence develop effective treatments these life-threatening conditions.

Language: Английский

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Emerging Viral Infections (ZIKV, SARS‐CoV‐2, and MPXV) and Depression: Ketamine and (S, R)‐Ketamine as Promising Antidepressants

Reviews in Medical Virology, Journal Year: 2025, Volume and Issue: 35(3)

Published: April 9, 2025

ABSTRACT Emerging viral pathogens, newly reported or rapidly evolving viruses, are a significant public health concern worldwide. Beyond their characteristic clinical presentations, emerging such as monkeypox virus (MPXV) and severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), have been increasingly implicated in the development of various neuropsychiatric complications including depression, mainly due to ability induce neuroinflammation, immune dysfunction, neurotransmitter imbalances. Depression is common mental condition characterised by continuous low mood sadness, pessimism, anxiety, even tendency suicide main symptoms. Post depression commonly shows challenges, traditional antidepressant agents exhibit suboptimal efficacy prolonged onset action. Regarding this, ketamine its enantiomers, S‐ketamine R‐ketamine, recently received increasing attention potential options light potent effective properties. The present review describes underlying pathophysiological mechanisms associated with highlighting role neuroinflammation disturbances inneurotransmitter systems. It also discusses current evidence demonstrating effectiveness safety, especially case treatment‐resistant growing relevance for linked infections, depression. Although preliminary reports propose effectiveness, additional studies needed optimal treatment strategies, long‐term incorporation into practice. Addressing these challenges will be critical optimising ketamine‐ (S, R)‐ketamine‐containing therapeutic protocols treating infections.

Language: Английский

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Gasdermin-D Genetic Knockout Reduces Inflammasome-Induced Disruption of the Gut-Brain Axis After Traumatic Brain Injury

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(8), P. 3512 - 3512

Published: April 9, 2025

Traumatic brain injury (TBI) pathology is significantly mediated by an inflammatory response involving inflammasome activation, resulting in the release of interleukin (IL)-1β and pyroptotic cell death through gasdermin-D (GSDMD) cleavage. Inflammasome components are transported extracellular vesicles (EVs) to mediate systemic inflammation peripheral organs, including gut. The purpose this study was determine protective effect GSDMD knockout (KO) on TBI-induced EV signaling, gut function. GSDMD-KO C57BL6 (WT) mice were subjected controlled cortical impact model TBI. Cytokine expression assessed with electrochemiluminescent immunoassay immunoblotting cerebral cortex EVs examined for pathology-associated markers using flow cytometry, permeability determined. attenuated IL-1β IL-6 reduced IL-18 3 days post-injury. had decreased neuronal- gut-derived compared WT post-TBI. also different surface marker after These data demonstrate that ablation improves post-TBI pathology, suggesting may serve as a potential therapeutic target improvement TBI-associated pathologies.

Language: Английский

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The role of pyroptosis in environmental pollutants-induced multisystem toxicities

Life Sciences, Journal Year: 2025, Volume and Issue: 372, P. 123632 - 123632

Published: April 10, 2025

Language: Английский

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Computational repurposing of polyphenols for anti-Mpoxviral activity

In Silico Pharmacology, Journal Year: 2025, Volume and Issue: 13(2)

Published: April 17, 2025

Abstract Mpox is a globally prevalent disease that has triggered multiple epidemics over the past few decades, leading to moderate rates of hospitalisation and mortality. Recently, it re-emerged in several countries, including Democratic Republic Congo, appears be spreading at an unprecedented pace. The caused by zoonotic double-stranded DNA viruses. Due its similarities with smallpox, distinguishing between two can challenging, though smallpox vaccine typically provides immunity against Mpox. At time writing, no approved treatment for exists; however, promising candidates have demonstrated ability inhibit viral replication, resveratrol—a polyphenolic compound found red wine. This study employs molecular docking dynamics simulations assess effectiveness stability nine resveratrol analogues. Additionally, 2D 3D pharmacophore models were developed highest-ranked docked compounds, composite pharmacophore. A structure–activity relationship analysis was also conducted using these top-performing compounds. findings suggest compounds— ( 9 ) [1,1'-biphenyl]-3,4',5-triol 11 {3-hydroxy-5-[2-(4-hydroxyphenyl)ethenyl]phenyl}oxidanesulfonic acid—exhibit strong binding affinity, potentially forming stable complex thymidylate kinase vaccinia virus. Graphical abstract

Language: Английский

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Drug screen reveals new potent host-targeted antivirals against Mpox virus

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: May 7, 2025

Mpox virus (MPXV), a re-emerging zoonotic threat, has caused outbreaks in non-endemic regions through respiratory, sexual, and close-contact transmission. The increased transmissibility of Clade IIb fueled the 2022 global outbreak, with 2024 Ib spread Democratic Republic Congo further escalating concern. Both were declared public health emergencies by WHO. Although tecovirimat (TPOXX) been used off-label for Mpox, its limited effectiveness highlights critical need newer antivirals MPXV. We conducted high- throughput antiviral drug screening using host-directed kinase inhibitor library composed 2,750 compounds against Our primary screen identified 138 preventing MPXV cytopathic effects, including multiple inhibitors EGFR, PI3K-mTOR, Ras/Raf, as well apoptosis autophagy regulators. Secondary tertiary screenings yielded shortlist potent, nontoxic that inhibited replication. Three selected compounds, IRAK4-IN-6, SM-7368, KRAS inhibitor-10, reduced MPXV-induced cell death human epidermal keratinocytes. IRAK4-IN-6 SM-7368 also found to modulate NF-κB STING signaling. Furthermore, these effective reducing skin lesions viral burden mouse model infection. Together, our study reveals new classes MPXV, offering promising candidates future clinical development.

Language: Английский

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Unveiling the role of gasdermin B in cancer and inflammatory disease: from molecular mechanisms to therapeutic strategies

PeerJ, Journal Year: 2025, Volume and Issue: 13, P. e19392 - e19392

Published: May 28, 2025

Gasdermin B (GSDMB) is a member of the gasdermin (GSDM) protein family, primarily known for mediating pyroptosis, an inflammatory form programmed cell death. Recent studies have revealed diverse molecular functions GSDMB and its close association with various diseases, particularly cancers ( e.g. , breast cancer, gastric bladder cancer) diseases asthma, bowel disease). At level, induces pyroptosis by forming pores in membrane, leading to membrane rupture. This function common across GSDM family; however, also exhibits unique non-pyroptotic functions, such as modulating proliferation, migration, immune responses. In multiple cancers, including cervical high expression correlates poor prognosis, promoting cancer invasion, metastasis through interactions signaling pathways STAT3 mitogen-activated kinase (MAPK)/extracellular signal-regulated (ERK). Additionally, influences microenvironment pyroptotic activity, playing role initiation regulation inflammation. Upon activation, it can directly cleave target cells via N-terminal domain, contributing significantly chronic NK cell-mediated antibacterial conclusion, multifunctional protein, not only participates but regulates processes, important progression diseases. Further elucidating detailed mechanisms may offer novel therapeutic avenues these conditions.

Language: Английский

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Re-visiting mpox: Stealth Assault on the Brain and Emerging Biomedical Research Insights

Brain Disorders, Journal Year: 2024, Volume and Issue: unknown, P. 100169 - 100169

Published: Oct. 1, 2024

Language: Английский

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Neurological Implications of Poxvirus Infections: Pathogenesis, Neurotropism, and Clinical Manifestations

Reviews in Medical Virology, Journal Year: 2024, Volume and Issue: 34(5)

Published: Sept. 1, 2024

Poxviridae is a diverse family of double-stranded DNA viruses, historically significant for diseases like smallpox caused by variola virus (VARV). These viruses exhibit unique cytoplasmic replication strategies, large genomes encoding numerous proteins, and the ability to cause severe cutaneous systemic diseases. Recent attention has focused on their neurotropic potential, including mechanisms CNS invasion, immune-mediated damage, clinical manifestations such as encephalitis myelitis. This review synthesises current knowledge poxvirus neurotropism, highlighting pathophysiological implications.

Language: Английский

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