Immune System Dysregulation in the Progression of Multiple Sclerosis: Molecular Insights and Therapeutic Implications

Khan, Zuber; Mehan, Sidharth; Gupta, Ghanshyam Das; Narula, Acharan S

doi:10.1016/j.neuroscience.2024.04.004

Cited by 3 publications

(2 citation statements)

References 212 publications

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“… 53 Overproduction of IFN‐γ can contribute to autoimmune disease pathology, including NMOSD and multiple sclerosis. 54 , 55 , 56 Thus, GV‐971's inhibition of IFN‐γ may reduce the immune response in the NMOSD model. IL‐12p40, a subunit shared by interleukin‐12 (IL‐12) and interleukin‐23 (IL‐23), plays a significant role in inflammatory responses and autoimmunity.…”

Section: Discussionmentioning

confidence: 99%

GV‐971 attenuates the progression of neuromyelitis optica in murine models and reverses alterations in gut microbiota and associated peripheral abnormalities

Yang,

Zhangyi,

et al. 2024

CNS Neurosci Ther

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AimsGrowing evidence suggests that an imbalanced gut microbiota composition plays a crucial role in the development of neuromyelitis optica spectrum disorders (NMOSD), an inflammatory demyelinating disease primarily affecting the optic nerves and central nervous system (CNS). In light of this, we explored the potential therapeutic benefits of GV‐971 in NMOSD. GV‐971 is a drug used for treating mild‐to‐moderate Alzheimer's disease, which targets the gut‐brain axis and reduces neuroinflammation.MethodsTo evaluate GV‐971's effects, we employed the experimental autoimmune encephalomyelitis (EAE) mouse model to establish NMOSD animal models. This was achieved by injecting NMO‐IgG into aged mice (11 months old) or using NMO‐IgG along with complement injection and microbubble‐enhanced low‐frequency ultrasound (MELFUS) techniques in young mice (7 weeks old). We assessed the impact of GV‐971 on incidence rate, clinical scores, body weight, and survival, with methylprednisolone serving as a positive control. In NMOSD models of young mice, we analyzed spinal cord samples through H&E staining, immunohistochemistry, and Luxol Fast Blue staining. Fecal samples collected at different time points underwent 16S rRNA gene sequencing, while plasma samples were analyzed using cytokine array and untargeted metabolomics analysis.ResultsOur findings indicated that GV‐971 significantly reduced the incidence of NMOSD, alleviated symptoms, and prolonged survival in NMOSD mouse models. The NMOSD model exhibited substantial neuroinflammation and injury, accompanied by imbalances in gut microbiota, peripheral inflammation, and metabolic disorders, suggesting a potentially vicious cycle that accelerates disease pathogenesis. Notably, GV‐971 effectively reduces neuroinflammation and injury, and restores gut microbiota composition, as well as ameliorates peripheral inflammation and metabolic disorders.ConclusionsGV‐971 attenuates the progression of NMOSD in murine models and reduces neuroinflammation and injury, likely through its effects on remodeling gut microbiota and peripheral inflammation and metabolic disorders.

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Section: Discussionmentioning

confidence: 99%

GV‐971 attenuates the progression of neuromyelitis optica in murine models and reverses alterations in gut microbiota and associated peripheral abnormalities

Yang,

Zhangyi,

et al. 2024

CNS Neurosci Ther

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“…Myelin demyelination is a pathogenic mechanism in MS. Myelin is produced by oligodendrocytes, and myelin oligodendrocyte glycoprotein (MOG) is a target of cellular and humoral immune responses in MS. MS has three subtypes: relapsing–remitting multiple sclerosis (RRMS), secondary progressive multiple sclerosis (SPMS), and primary progressive multiple sclerosis (PPMS) [ 56 , 57 , 58 ]. MOG is the most immunogenic myelin phospholipid protein, and anti-MOG antibodies can lead to myelin destruction [ 59 , 60 ]; MOG is significantly increased in serum exosomes from patients with relapsing–remitting RRMS and patients with SPMS [ 61 ]. Fibroblast growth factor-2 (FGF-2) has been implicated in myelin destruction and regeneration, and FGF-2 in cerebrospinal fluid (CSF) can be used as a diagnostic biomarker for MS [ 62 , 63 ].…”

Section: Exosomes In the Diagnosis Of Demyelinating Diseasesmentioning

confidence: 99%

Exosomes in the Diagnosis of Neuropsychiatric Diseases: A Review

Wu,

Shang,

Guo

et al. 2024

Biology

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Exosomes are 30–150 nm small extracellular vesicles (sEVs) which are highly stable and encapsulated by a phospholipid bilayer. Exosomes contain proteins, lipids, RNAs (mRNAs, microRNAs/miRNAs, long non-coding RNAs/lncRNAs), and DNA of their parent cell. In pathological conditions, the composition of exosomes is altered, making exosomes a potential source of biomarkers for disease diagnosis. Exosomes can cross the blood–brain barrier (BBB), which is an advantage for using exosomes in the diagnosis of central nervous system (CNS) diseases. Neuropsychiatric diseases belong to the CNS diseases, and many potential diagnostic markers have been identified for neuropsychiatric diseases. Here, we review the potential diagnostic markers of exosomes in neuropsychiatric diseases and discuss the potential application of exosomal biomarkers in the early and accurate diagnosis of these diseases. Additionally, we outline the limitations and future directions of exosomes in the diagnosis of neuropsychiatric diseases.

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Can International Classification of Functioning, Disability and Health (ICF) Be Used for Prediction of Work Capacity and Employment Status in Multiple Sclerosis?

Valadkevičienė,

Jatužis,

Žukauskaitė

et al. 2024

JCM

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Background: Multiple sclerosis (MS) affects many body functions and activities, including work capacity and ability to work. An evaluation of work-related parameters is important to understand the barriers to maintaining the job. The aim of this study was to evaluate if a Comprehensive International Classification of Functioning, Disability and Health (ICF) core set for MS can be used to predict work capacity and employment status. Methods: The cohort included 151 participants with MS (99 female/52 male, mean age 49 years) referred for a work capacity evaluation. Results: 71 (47.0%) were employed and a major part (131, 86.7%) had a work capacity between 20 and 40% with no difference between those who were employed and those who were unemployed. The analysis revealed that age and the following categories explained 68.8% of the work capacity: b770 Gait pattern functions; b730 Muscle power functions; b134 Sleep functions; d845 Acquiring, keeping and terminating a job; and b620 Urination functions. The following categories in 79.5% predicted ability to work: b164 Higher-level cognitive functions; d510 Washing oneself; d630; Preparing meals; and d870 Economic self-sufficiency. Conclusions: Here, we show that different functions/activities predicted work capacity in comparison with employment status in MS. Therefore, ICF should be implemented when assessing work ability.

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Immune System Dysregulation in the Progression of Multiple Sclerosis: Molecular Insights and Therapeutic Implications

Cited by 3 publications

References 212 publications

GV‐971 attenuates the progression of neuromyelitis optica in murine models and reverses alterations in gut microbiota and associated peripheral abnormalities

GV‐971 attenuates the progression of neuromyelitis optica in murine models and reverses alterations in gut microbiota and associated peripheral abnormalities

Exosomes in the Diagnosis of Neuropsychiatric Diseases: A Review

Can International Classification of Functioning, Disability and Health (ICF) Be Used for Prediction of Work Capacity and Employment Status in Multiple Sclerosis?

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