Molecular Mechanisms of Neurological Autoimmune Disorders

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Neurobiology and Clinical Neuroscience".

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 21624

Special Issue Editors


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Guest Editor
Neurology IV–Neuroimmunology and Neuromuscular Diseases Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Via Celoria 11, 20133 Milan, Italy
Interests: neuroimmunology, autoantibodies, neuromuscular diseases, myasthenia gravis, multiple sclerosis
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
Neurology IV–Neuroimmunology and Neuromuscular Diseases Unit, Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta, 20133 Milan, Italy
Interests: autoimmunity; inflammation; innate immunity; microRNAs; myasthenia gravis; neuroimmunology; pharmacogenetics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Neurological autoimmune disorders are a broad and heterogenous group of autoimmune diseases affecting the central (i.e., brain, spinal cord, CNS) and peripheral (i.e., peripheral nerves, neuromuscular junction, skeletal muscle, PNS) nervous systems, leading to a wide spectrum of symptoms and multifaceted clinical manifestations. They include demyelinating disorders such as multiple sclerosis (MS) and neuromyelitis optica (NMO), autoimmune encephalitis, Guillain–Barrè syndrome, and myasthenia gravis (MG). MG is widely considered a prototypic autoimmune disease, due to the well-known role of autoantibodies for neuromuscular junction proteins as a cause of the disease. The discovery of autoantibodies for neuronal or glial targets is still an open research field, which may allow for gaining a major understanding of CNS autoimmunity, with relevant clinical implications.

This Special Issue aims to increase scientific knowledge on the pathogenic mechanisms underlying autoimmunity in neurological diseases, including MS, NMO, autoimmune encephalitis, Guillain–Barrè syndrome, and MG. It will be focused on the role of autoantibodies, and on genetic and environmental (e.g., infections) risk factors associated with autoimmunity development. Original data on the contribution of neuroinflammation, as well as on central and peripheral immune system cell (e.g., innate immune system cell, T and B cell) alterations, will be collected. Manuscripts providing insights on non-coding RNAs as molecular factors implicated in immune tolerance breakdown, or clinical biomarkers for these disorders, are also welcome.

New findings on the molecular events leading to CNS and PNS autoimmune disorders will promote translational research, paving the way for the development of more specific and effective therapies for the treatment of these conditions.

Dr. Francesca Andreetta
Dr. Paola Cavalcante
Guest Editors

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Keywords

  • neurological autoimmune disorders
  • multiple sclerosis
  • neuromyelitis optica
  • autoimmune encephalitis
  • Guillain–Barrè syndrome
  • myasthenia gravis
  • autoantibodies
  • neuroinflammation
  • innate and adaptive immune systems
  • non-coding RNAs

Published Papers (10 papers)

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Research

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18 pages, 2304 KiB  
Article
Muscle and Muscle-like Autoantigen Expression in Myasthenia Gravis Thymus: Possible Molecular Hint for Autosensitization
by Nicola Iacomino, Letizia Scandiffio, Fabio Conforti, Erika Salvi, Maria Cristina Tarasco, Federica Bortone, Stefania Marcuzzo, Ornella Simoncini, Francesca Andreetta, Daniela Pistillo, Emanuele Voulaz, Marco Alloisio, Carlo Antozzi, Renato Mantegazza, Tommaso Martino De Pas and Paola Cavalcante
Biomedicines 2023, 11(3), 732; https://doi.org/10.3390/biomedicines11030732 - 28 Feb 2023
Cited by 4 | Viewed by 1649
Abstract
The thymus is widely recognized as an immunological niche where autoimmunity against the acetylcholine receptor (AChR) develops in myasthenia gravis (MG) patients, who mostly present thymic hyperplasia and thymoma. Thymoma-associated MG is frequently characterized by autoantibodies to the muscular ryanodine receptor 1 (RYR1) [...] Read more.
The thymus is widely recognized as an immunological niche where autoimmunity against the acetylcholine receptor (AChR) develops in myasthenia gravis (MG) patients, who mostly present thymic hyperplasia and thymoma. Thymoma-associated MG is frequently characterized by autoantibodies to the muscular ryanodine receptor 1 (RYR1) and titin (TTN), along with anti-AChR antibodies. By real-time PCR, we analyzed muscle—CHRNA1, RYR1, and TTN—and muscle-like—NEFM, RYR3 and HSP60—autoantigen gene expression in MG thymuses with hyperplasia and thymoma, normal thymuses and non-MG thymomas, to check for molecular changes potentially leading to an altered antigen presentation and autoreactivity. We found that CHRNA1 (AChR-α subunit) and AIRE (autoimmune regulator) genes were expressed at lower levels in hyperplastic and thymoma MG compared to the control thymuses, and that the RYR1 and TTN levels were decreased in MG versus the non-MG thymomas. Genes encoding autoantigens that share epitopes with AChR-α (NEFM and HSP60), RYR1 (neuronal RYR3), and TTN (NEFM) were up-regulated in thymomas versus hyperplastic and control thymuses, with distinct molecular patterns across the thymoma histotypes that could be relevant for autoimmunity development. Our findings support the idea that altered muscle autoantigen expression, related with hyperplastic and neoplastic changes, may favor autosensitization in the MG thymus, and that molecular mimicry involving tumor-related muscle-like proteins may be a mechanism that makes thymoma prone to developing MG. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Neurological Autoimmune Disorders)
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11 pages, 402 KiB  
Article
Serum Neurofilaments and OCT Metrics Predict EDSS-Plus Score Progression in Early Relapse-Remitting Multiple Sclerosis
by Vlad Eugen Tiu, Bogdan Ovidiu Popescu, Iulian Ion Enache, Cristina Tiu, Alina Popa Cherecheanu and Cristina Aura Panea
Biomedicines 2023, 11(2), 606; https://doi.org/10.3390/biomedicines11020606 - 17 Feb 2023
Cited by 2 | Viewed by 1452
Abstract
(1) Background: Early disability accrual in RRMS patients is frequent and is associated with worse long-term prognosis. Correctly identifying the patients that present a high risk of early disability progression is of utmost importance, and may be aided by the use of predictive [...] Read more.
(1) Background: Early disability accrual in RRMS patients is frequent and is associated with worse long-term prognosis. Correctly identifying the patients that present a high risk of early disability progression is of utmost importance, and may be aided by the use of predictive biomarkers. (2) Methods: We performed a prospective cohort study that included newly diagnosed RRMS patients, with a minimum follow-up period of one year. Biomarker samples were collected at baseline, 3-, 6- and 12-month follow-ups. Disability progression was measured using the EDSS-plus score. (3) Results: A logistic regression model based on baseline and 6-month follow-up sNfL z-scores, RNFL and GCL-IPL thickness and BREMSO score was statistically significant, with χ2(4) = 19.542, p < 0.0001, R2 = 0.791. The model correctly classified 89.1% of cases, with a sensitivity of 80%, a specificity of 93.5%, a positive predictive value of 85.7% and a negative predictive value of 90.62%. (4) Conclusions: Serum biomarkers (adjusted sNfL z-scores at baseline and 6 months) combined with OCT metrics (RNFL and GCL-IPL layer thickness) and the clinical score BREMSO can accurately predict early disability progression using the EDSS-plus score for newly diagnosed RRMS patients. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Neurological Autoimmune Disorders)
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17 pages, 3083 KiB  
Article
Immunological and Structural Characterization of Titin Main Immunogenic Region; I110 Domain Is the Target of Titin Antibodies in Myasthenia Gravis
by Christos Stergiou, Rhys Williams, Jennifer R. Fleming, Vasiliki Zouvelou, Elpinickie Ninou, Francesca Andreetta, Elena Rinaldi, Ornella Simoncini, Renato Mantegazza, Julius Bogomolovas, John Tzartos, Siegfried Labeit, Olga Mayans and Socrates Tzartos
Biomedicines 2023, 11(2), 449; https://doi.org/10.3390/biomedicines11020449 - 3 Feb 2023
Cited by 2 | Viewed by 2004
Abstract
Myasthenia gravis (MG) is an autoimmune disease caused by antibodies targeting the neuromuscular junction (NJ) of skeletal muscles. The major MG autoantigen is nicotinic acetylcholine receptor. Other autoantigens at the NJ include MuSK, LRP4 and agrin. Autoantibodies to the intra-sarcomeric striated muscle-specific gigantic [...] Read more.
Myasthenia gravis (MG) is an autoimmune disease caused by antibodies targeting the neuromuscular junction (NJ) of skeletal muscles. The major MG autoantigen is nicotinic acetylcholine receptor. Other autoantigens at the NJ include MuSK, LRP4 and agrin. Autoantibodies to the intra-sarcomeric striated muscle-specific gigantic protein titin, although not directed to the NJ, are invaluable biomarkers for thymoma and MG disease severity. Thymus and thymoma are critical in MG mechanisms and management. Titin autoantibodies bind to a 30 KDa titin segment, the main immunogenic region (MIR), consisting of an Ig-FnIII-FnIII 3-domain tandem, termed I109–I111. In this work, we further resolved the localization of titin epitope(s) to facilitate the development of more specific anti-titin diagnostics. For this, we expressed protein samples corresponding to 8 MIR and non-MIR titin fragments and tested 77 anti-titin sera for antibody binding using ELISA, competition experiments and Western blots. All anti-MIR antibodies were bound exclusively to the central MIR domain, I110, and to its containing titin segments. Most antibodies were bound also to SDS-denatured I110 on Western blots, suggesting that their epitope(s) are non-conformational. No significant difference was observed between thymoma and non-thymoma patients or between early- and late-onset MG. In addition, atomic 3D-structures of the MIR and its subcomponents were elucidated using X-ray crystallography. These immunological and structural data will allow further studies into the atomic determinants underlying titin-based autoimmunity, improved diagnostics and how to eventually treat titin autoimmunity associated co-morbidities. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Neurological Autoimmune Disorders)
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27 pages, 4743 KiB  
Article
Beta-Boswellic Acid Reverses 3-Nitropropionic Acid-Induced Molecular, Mitochondrial, and Histopathological Defects in Experimental Rat Model of Huntington’s Disease
by Thamer H. Albekairi, Arzoo Kamra, Sudeep Bhardwaj, Sidharth Mehan, Aditi Giri, Manisha Suri, Abdulrahman Alshammari, Metab Alharbi, Abdullah F. Alasmari, Acharan S Narula and Reni Kalfin
Biomedicines 2022, 10(11), 2866; https://doi.org/10.3390/biomedicines10112866 - 9 Nov 2022
Cited by 7 | Viewed by 2163
Abstract
Huntington’s disease (HD) is distinguished by a triple repeat of CAG in exon 1, an increase in poly Q in the Htt gene, and a loss of GABAergic medium spiny neurons (MSN) in the striatum and white matter of the cortex. Mitochondrial ETC-complex [...] Read more.
Huntington’s disease (HD) is distinguished by a triple repeat of CAG in exon 1, an increase in poly Q in the Htt gene, and a loss of GABAergic medium spiny neurons (MSN) in the striatum and white matter of the cortex. Mitochondrial ETC-complex dysfunctions are involved in the pathogenesis of HD, including neuronal energy loss, synaptic neurotrophic decline, neuronal inflammation, apoptosis, and grey and white matter destruction. A previous study has demonstrated that beta Boswellic acid (β-BA), a naturally occurring phytochemical, has several neuroprotective properties that can reduce pathogenic factors associated with various neurological disorders. The current investigation aimed to investigate the neuroprotective potential of β-BA at oral doses of 5, 10, and 15 mg/kg alone, as well as in conjunction with the potent antioxidant vitamin E (8 mg/kg, orally) in 3-NP-induced experimental HD rats. Adult Wistar rats were separated into seven groups, and 3-NP, at a dose of 10 mg/kg, was orally administered to each group of adult Wistar rats beginning on day 1 and continuing through day 14. The neurotoxin 3-NP induces neurodegenerative, g, neurochemical, and pathological alterations in experimental animals. Continuous injection of 3-NP, according to our results, aggravated HD symptoms by suppressing ETC-complex-II, succinate dehydrogenase activity, and neurochemical alterations. β-BA, when taken with vitamin E, improved behavioural dysfunctions such as neuromuscular and motor impairments, as well as memory and cognitive abnormalities. Pharmacological treatments with β-BA improved and restored ETC complexes enzymes I, II, and V levels in brain homogenates. β-BA treatment also restored neurotransmitter levels in the brain while lowering inflammatory cytokines and oxidative stress biomarkers. β-BA’s neuroprotective potential in reducing neuronal death was supported by histopathological findings in the striatum and cortex. As a result, the findings of this research contributed to a better understanding of the potential role of natural phytochemicals β-BA in preventing neurological illnesses such as HD. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Neurological Autoimmune Disorders)
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9 pages, 1140 KiB  
Communication
Anti-Cyclic Citrullinated Peptide Antibody Index in the Cerebrospinal Fluid for the Diagnosis and Monitoring of Rheumatoid Meningitis
by Luigi Caputi, Giorgio B. Boncoraglio, Gaetano Bernardi, Emilio Ciusani, Marcello Dantes, Federica de Liso, Alessandra Erbetta, Gianluca Marucci, Caterina Matinato and Elena Corsini
Biomedicines 2022, 10(10), 2401; https://doi.org/10.3390/biomedicines10102401 - 26 Sep 2022
Cited by 3 | Viewed by 1235
Abstract
Rheumatoid meningitis (RM) is a rare but often aggressive neurological complication of rheumatoid arthritis. The diagnosis of RM, besides the clinical, radiological, and laboratory criteria, usually requires a cerebral biopsy. Based on the two cases presented in this paper, we propose a new [...] Read more.
Rheumatoid meningitis (RM) is a rare but often aggressive neurological complication of rheumatoid arthritis. The diagnosis of RM, besides the clinical, radiological, and laboratory criteria, usually requires a cerebral biopsy. Based on the two cases presented in this paper, we propose a new laboratory marker. Cerebrospinal fluid and serum anti-cyclic citrullinated peptide (CCP) IgG were measured, and the intrathecal synthesis of anti-CCP antibodies (anti-CCP antibody index) was calculated using the hyperbolic function. The anti-CCP antibody index was positive in both cases at first diagnosis and progressively decreased after treatments. Together with clinical and radiological criteria, the calculation of the anti-CCP intrathecal synthesis, more than the simple measurement of serum or cerebrospinal fluid anti-CCP antibody titers, may represent a useful tool for RM diagnosis and, possibly, for treatment response. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Neurological Autoimmune Disorders)
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14 pages, 2624 KiB  
Article
Role of Cytokines, Chemokines and IFN-γ+ IL-17+ Double-Positive CD4+ T Cells in Patients with Multiple Sclerosis
by Marlos Aureliano Dias de Sousa, Chamberttan Souza Desidério, Jonatas da Silva Catarino, Rafael Obata Trevisan, Djalma Alexandre Alves da Silva, Vinicius Ferreira Resende Rocha, Weslley Guimarães Bovi, Rodolfo Pessato Timoteo, Renata Cristina Franzon Bonatti, Alex Eduardo da Silva, Alfredo Leboreiro Fernandez, Helioswilton Sales-Campos, Virmondes Rodrigues Junior, Marcos Vinicius da Silva and Carlo José Freire de Oliveira
Biomedicines 2022, 10(9), 2062; https://doi.org/10.3390/biomedicines10092062 - 24 Aug 2022
Cited by 5 | Viewed by 2207
Abstract
Multiple sclerosis is mediated by self-reactive myelin T and B cells that lead to axonal and myelin damage. The immune response in multiple sclerosis involves the participation of CD4+ T cells that produce cytokines and chemokines. This participation is important to find [...] Read more.
Multiple sclerosis is mediated by self-reactive myelin T and B cells that lead to axonal and myelin damage. The immune response in multiple sclerosis involves the participation of CD4+ T cells that produce cytokines and chemokines. This participation is important to find markers for the diagnosis and progression of the disease. In our work, we evaluated the profile of cytokines and chemokines, as well as the production of double positive CD4+ T cells for the production of IFNγ IL-17 in patients with multiple sclerosis, at different stages of the disease and undergoing different treatments. We found that relapsing–remitting patients had a significant increase in IL-12 production. About IL-5, its production showed significantly higher levels in secondarily progressive patients when compared to relapsing–remitting patients. IFN-γ production by PBMCs from secondarily progressive patients showed significantly higher levels. This group also had a higher percentage of CD4+ IFNγ+ IL-17+ T cells. The combination of changes in certain cytokines and chemokines together with the presence of IFNγ+ IL-17+ double positive lymphocytes can be used to better understand the clinical forms of the disease and its progression. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Neurological Autoimmune Disorders)
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15 pages, 2757 KiB  
Article
Human Primary Astrocytes Differently Respond to Pro- and Anti-Inflammatory Stimuli
by Piotr Szpakowski, Dominika Ksiazek-Winiarek, Malgorzata Turniak-Kusy, Ilona Pacan and Andrzej Glabinski
Biomedicines 2022, 10(8), 1769; https://doi.org/10.3390/biomedicines10081769 - 22 Jul 2022
Cited by 11 | Viewed by 2610
Abstract
For a long time, astrocytes were considered a passive brain cell population. However, recently, many studies have shown that their role in the central nervous system (CNS) is more active. Previously, it was stated that there are two main functional phenotypes of astrocytes. [...] Read more.
For a long time, astrocytes were considered a passive brain cell population. However, recently, many studies have shown that their role in the central nervous system (CNS) is more active. Previously, it was stated that there are two main functional phenotypes of astrocytes. However, nowadays, it is clear that there is rather a broad spectrum of these phenotypes. The major goal of this study was to evaluate the production of some inflammatory chemokines and neurotrophic factors by primary human astrocytes after pro- or anti-inflammatory stimulation. We observed that only astrocytes induced by inflammatory mediators TNFα/IL-1a/C1q produced CXCL10, CCL1, and CXCL13 chemokines. Unstimulated astrocytes and those cultured with anti-inflammatory cytokines (IL-4, IL-10, or TGF-β1) did not produce these chemokines. Interestingly, astrocytes cultured in proinflammatory conditions significantly decreased the release of neurotrophic factor PDGF-A, as compared to unstimulated astrocytes. However, in response to anti-inflammatory cytokine TGF-β1, astrocytes significantly increased PDGF-A production compared to the medium alone. The production of another studied neurotrophic factor BDNF was not influenced by pro- or anti-inflammatory stimulation. The secretory response was accompanied by changes in HLA-DR, CD83, and GFAP expression. Our study confirms that astrocytes differentially respond to pro- and anti-inflammatory stimuli, especially to inflammatory cytokines TNF-α, IL-1a, and C1q, suggesting their role in leukocyte recruitment. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Neurological Autoimmune Disorders)
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12 pages, 1814 KiB  
Article
Antihuman Endogenous Retrovirus Immune Response and Adaptive Dysfunction in Autism
by Alessandra Carta, Maria Antonietta Manca, Chiara Scoppola, Elena Rita Simula, Marta Noli, Stefano Ruberto, Marta Conti, Ignazio Roberto Zarbo, Roberto Antonucci, Leonardo A. Sechi and Stefano Sotgiu
Biomedicines 2022, 10(6), 1365; https://doi.org/10.3390/biomedicines10061365 - 9 Jun 2022
Cited by 2 | Viewed by 1878
Abstract
ASD is a neurodevelopmental disorder of unknown aetiology but with a known contribution of pathogenic immune-mediated mechanisms. HERVs are associated with several neuropsychiatric diseases, including ASD. We studied anti-HERV-W, -K and -H-env immune profiles in ASD children to analyse differences between their respective [...] Read more.
ASD is a neurodevelopmental disorder of unknown aetiology but with a known contribution of pathogenic immune-mediated mechanisms. HERVs are associated with several neuropsychiatric diseases, including ASD. We studied anti-HERV-W, -K and -H-env immune profiles in ASD children to analyse differences between their respective mothers and child/mother control pairs and possible correlations to ASD severity and loss of adaptive abilities. Of the 84 studied individuals, 42 children (23 ASD and 19 neurotypical) and their paired mothers underwent clinical and neuropsychological evaluations. ASD severity was analysed with standardised tests. Adaptive functioning was studied with ABAS-II and GAC index. Plasma anti-env responses of HERV-K, -H and -W were tested with indirect ELISA. ASD and neurotypical children did not differ in age, gender, comorbidities and anti-HERV responses. In children with ASD, anti-HERV levels were not correlated to ASD severity, while a significant inverse correlation was found between anti-HERV-W-248-262 levels and adaptive/social abilities. Upregulation of anti-HERV-W response correlates to dysfunctional social and adaptive competences in ASD but not in controls, suggesting anti-HERV response plays a role in the appearance of peculiar ASD symptoms. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Neurological Autoimmune Disorders)
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12 pages, 2196 KiB  
Article
Complement Activation Profile in Myasthenia Gravis Patients: Perspectives for Tailoring Anti-Complement Therapy
by Nicola Iacomino, Fiammetta Vanoli, Rita Frangiamore, Marta Ballardini, Letizia Scandiffio, Federica Bortone, Francesca Andreetta, Fulvio Baggi, Pia Bernasconi, Carlo Antozzi, Paola Cavalcante and Renato Mantegazza
Biomedicines 2022, 10(6), 1360; https://doi.org/10.3390/biomedicines10061360 - 9 Jun 2022
Cited by 4 | Viewed by 2647
Abstract
The complement system plays a key role in myasthenia gravis (MG). Anti-complement drugs are emerging as effective therapies to treat anti-acetylcholine receptor (AChR) antibody-positive MG patients, though their usage is still limited by the high costs. Here, we searched for plasma complement proteins [...] Read more.
The complement system plays a key role in myasthenia gravis (MG). Anti-complement drugs are emerging as effective therapies to treat anti-acetylcholine receptor (AChR) antibody-positive MG patients, though their usage is still limited by the high costs. Here, we searched for plasma complement proteins as indicators of complement activation status in AChR-MG patients, and potential biomarkers for tailoring anti-complement therapy in MG. Plasma was collected from AChR-MG and MuSK-MG patients, and healthy controls. Multiplex immunoassays and ELISA were used to quantify a panel of complement components (C1Q, C2, C3, C4, C5, Factor B, Factor H, MBL, and properdin) and activation products (C4b, C3b, C5a, and C5b-9), of classical, alternative and lectin pathways. C2 and C5 levels were significantly reduced, and C3, C3b, and C5a increased, in plasma of AChR-MG, but not MuSK-MG, patients compared to controls. This protein profile was indicative of complement activation. We obtained sensitivity and specificity performance results suggesting plasma C2, C3, C3b, and C5 as biomarkers for AChR-MG. Our findings reveal a plasma complement “C2, C3, C5, C3b, and C5a” profile associated with AChR-MG to be further investigated as a biomarker of complement activation status in AChR-MG patients, opening new perspectives for tailoring of anti-complement therapies to improve the disease treatment. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Neurological Autoimmune Disorders)
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Review

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22 pages, 1425 KiB  
Review
Gut Dysbiosis and Blood-Brain Barrier Alteration in Hepatic Encephalopathy: From Gut to Brain
by Ali Shahbazi, Ali Sepehrinezhad, Edris Vahdani, Raika Jamali, Monireh Ghasempour, Shirin Massoudian, Sajad Sahab Negah and Fin Stolze Larsen
Biomedicines 2023, 11(5), 1272; https://doi.org/10.3390/biomedicines11051272 - 25 Apr 2023
Cited by 3 | Viewed by 2306
Abstract
A common neuropsychiatric complication of advanced liver disease, hepatic encephalopathy (HE), impacts the quality of life and length of hospital stays. There is new evidence that gut microbiota plays a significant role in brain development and cerebral homeostasis. Microbiota metabolites are providing a [...] Read more.
A common neuropsychiatric complication of advanced liver disease, hepatic encephalopathy (HE), impacts the quality of life and length of hospital stays. There is new evidence that gut microbiota plays a significant role in brain development and cerebral homeostasis. Microbiota metabolites are providing a new avenue of therapeutic options for several neurological-related disorders. For instance, the gut microbiota composition and blood-brain barrier (BBB) integrity are altered in HE in a variety of clinical and experimental studies. Furthermore, probiotics, prebiotics, antibiotics, and fecal microbiota transplantation have been shown to positively affect BBB integrity in disease models that are potentially extendable to HE by targeting gut microbiota. However, the mechanisms that underlie microbiota dysbiosis and its effects on the BBB are still unclear in HE. To this end, the aim of this review was to summarize the clinical and experimental evidence of gut dysbiosis and BBB disruption in HE and a possible mechanism. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Neurological Autoimmune Disorders)
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