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Biomedicines
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Immune Dysfunction in Brain Disorders
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Immune Dysfunction in Brain Disorders

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Immunology and Immunotherapy".

Deadline for manuscript submissions: closed (31 December 2023) | Viewed by 18580

Special Issue Editor

Dr. Luca Pangrazzi

E-Mail Website
Guest Editor
Institute for Biomedical Aging Research, University of Innsbruck, 6020 Innsbruck, Austria
Interests: immunosenescence; ageing; senolytics; T-cells but not B-cells
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Immune system dysfunction is known to contribute to the pathogenesis and severity of brain disorders. Impairments in the production of pro-inflammatory mediators, as well as in the secretion of chemokines regulating the migration of immune cells, have been associated with a broad spectrum of brain disorders, including neurodevelopmental disorders, Parkinson’s disease, Alzheimer’s diseases, and brain tumors. Furthermore, pro-inflammatory molecules may impair brain physiology during aging, therefore contributing to age-related dementia. The aim of this Special Issue is therefore to describe the role of inflammation in the pathogenesis and severity of brain disorders. In addition, manuscripts which aim to discuss the contribution of brain damage to the onset of pro-inflammatory conditions are welcome.

Dr. Luca Pangrazzi
Guest Editor

Manuscript Submission Information

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Keywords

  • inflammation
  • brain
  • damage
  • autism
  • aging
  • Alzheimer's disease
  • Parkinson's disease

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Published Papers (5 papers)

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Research

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19 pages, 597 KiB  
Article
Natural IgG Anti-F (ab’)2 Autoantibody Activity in Children with Autism
by Sylvie Tordjman, Annaëlle Charrier, Michel Kazatchkine, Pierre Roubertoux, Michel Botbol, Guillaume Bronsard and Stratis Avrameas
Biomedicines 2023, 11(3), 715; https://doi.org/10.3390/biomedicines11030715 - 27 Feb 2023
Cited by 1 | Viewed by 2043
Abstract
Background: Many and diverse autoimmune abnormalities have been reported in children with autism. Natural autoantibodies (NAAbs) play important immunoregulatory roles in recognition of the immune self. The objective of this study was to examine the presence of NAAbs in the sera of children [...] Read more.
Background: Many and diverse autoimmune abnormalities have been reported in children with autism. Natural autoantibodies (NAAbs) play important immunoregulatory roles in recognition of the immune self. The objective of this study was to examine the presence of NAAbs in the sera of children with autism and across severity subgroups of autistic behavioral impairments. Methods: NAAbs were titrated in sera through an ELISA procedure in 60 low-functioning children with autism and 112 typically developing controls matched for age, sex and puberty. Results: Serum titers of IgG anti-F(ab’)2 autoantibodies were significantly lower in children with autism compared to typically developing controls (p < 0.0001), and were significantly negatively associated with autism severity (p = 0.0001). This data appears to be related more specifically to autism than to intellectual disability, given that IgG anti-F(ab’)2 levels were significantly negatively correlated with IQ scores in the autism group (p = 0.01). Conclusions: This is the first report in autism of abnormally low natural anti-F(ab’)2 autoantibody activity. The findings suggest a dysfunction of self-recognition mechanisms which may play a role in the pathogenesis of autism, especially for the severely affected children. These findings strengthen the hypothesis of an autoimmune process in autism and open the prospect of alternative medical treatment. Further neuroimmunological research is warranted to understand the exact mechanisms underlying this reduced natural IgG anti-F (ab’)2 autoantibody activity, and to assess its impact on the pathophysiology and behavioral expression of autism. Full article
(This article belongs to the Special Issue Immune Dysfunction in Brain Disorders)
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28 pages, 5612 KiB  
Article
Activity of a Novel Anti-Inflammatory Agent F-3,6′-dithiopomalidomide as a Treatment for Traumatic Brain Injury
by Shih Chang Hsueh, Michael T. Scerba, David Tweedie, Daniela Lecca, Dong Seok Kim, Abdul Mannan Baig, Yu Kyung Kim, Inho Hwang, Sun Kim, Warren R. Selman, Barry J. Hoffer and Nigel H. Greig
Biomedicines 2022, 10(10), 2449; https://doi.org/10.3390/biomedicines10102449 - 30 Sep 2022
Cited by 5 | Viewed by 3580
Abstract
Traumatic brain injury (TBI) is a major risk factor for several neurodegenerative disorders, including Parkinson’s disease (PD) and Alzheimer’s disease (AD). Neuroinflammation is a cause of later secondary cell death following TBI, has the potential to aggravate the initial impact, and provides a [...] Read more.
Traumatic brain injury (TBI) is a major risk factor for several neurodegenerative disorders, including Parkinson’s disease (PD) and Alzheimer’s disease (AD). Neuroinflammation is a cause of later secondary cell death following TBI, has the potential to aggravate the initial impact, and provides a therapeutic target, albeit that has failed to translate into clinical trial success. Thalidomide-like compounds have neuroinflammation reduction properties across cellular and animal models of TBI and neurodegenerative disorders. They lower the generation of proinflammatory cytokines, particularly TNF-α which is pivotal in microglial cell activation. Unfortunately, thalidomide-like drugs possess adverse effects in humans before achieving anti-inflammatory drug levels. We developed F-3,6′-dithiopomalidomide (F-3,6′-DP) as a novel thalidomide-like compound to ameliorate inflammation. F-3,6′-DP binds to cereblon but does not efficiently trigger the degradation of the transcription factors (SALL4, Ikaros, and Aiolos) associated with the teratogenic and anti-proliferative responses of thalidomide-like drugs. We utilized a phenotypic drug discovery approach that employed cellular and animal models in the selection and development of F-3,6’-DP. F-3,6′-DP significantly mitigated LPS-induced inflammatory markers in RAW 264.7 cells, and lowered proinflammatory cytokine/chemokine levels in the plasma and brain of rats challenged with systemic LPS. We subsequently examined immunohistochemical, biochemical, and behavioral measures following controlled cortical impact (CCI) in mice, a model of moderate TBI known to induce inflammation. F-3,6′-DP decreased CCI-induced neuroinflammation, neuronal loss, and behavioral deficits when administered after TBI. F-3,6′-DP represents a novel class of thalidomide-like drugs that do not lower classical cereblon-associated transcription factors but retain anti-inflammatory actions and possess efficacy in the treatment of TBI and potentially longer-term neurodegenerative disorders. Full article
(This article belongs to the Special Issue Immune Dysfunction in Brain Disorders)
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Review

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20 pages, 1336 KiB  
Review
The Role of Dietary Lipids in Cognitive Health: Implications for Neurodegenerative Disease
by Sakshi Hans, Alexandra Karadimou, John J. E. Mulvihill, Andreas M. Grabrucker and Ioannis Zabetakis
Biomedicines 2022, 10(12), 3250; https://doi.org/10.3390/biomedicines10123250 - 14 Dec 2022
Cited by 8 | Viewed by 4553
Abstract
Neurodegenerative diseases are a group of disorders characterised by progressive loss of brain function. The most common of these is Alzheimer’s disease, a form of dementia. Intake of macro- and micro-nutrients impacts brain function, including memory, learning, mood, and behaviour. Lipids, particularly phospholipids [...] Read more.
Neurodegenerative diseases are a group of disorders characterised by progressive loss of brain function. The most common of these is Alzheimer’s disease, a form of dementia. Intake of macro- and micro-nutrients impacts brain function, including memory, learning, mood, and behaviour. Lipids, particularly phospholipids and sphingolipids, are crucial structural components of neural tissues and significantly affect cognitive function. The importance of functional foods in preventing cardiovascular disease is well-documented in the current literature. However, the significance of such foods for central nervous system health and neurodegenerative diseases is less recognized. Gut microbiome composition affects cognitive health and function, and dietary lipids are known to influence gut health. Thus, this review will discuss different sources of dietary lipids and their effect on cognitive functioning and their interaction with the gut microbiome in the context of neurodegenerative disease. Full article
(This article belongs to the Special Issue Immune Dysfunction in Brain Disorders)
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16 pages, 973 KiB  
Review
Sex Hormones as Key Modulators of the Immune Response in Multiple Sclerosis: A Review
by Federica Murgia, Florianna Giagnoni, Lorena Lorefice, Paola Caria, Tinuccia Dettori, Maurizio N. D’Alterio, Stefano Angioni, Aran J. Hendren, Pierluigi Caboni, Monica Pibiri, Giovanni Monni, Eleonora Cocco and Luigi Atzori
Biomedicines 2022, 10(12), 3107; https://doi.org/10.3390/biomedicines10123107 - 1 Dec 2022
Cited by 14 | Viewed by 4429
Abstract
Background: A variety of autoimmune diseases, including MS, amplify sex-based physiological differences in immunological responsiveness. Female MS patients experience pathophysiological changes during reproductive phases (pregnancy and menopause). Sex hormones can act on immune cells, potentially enabling them to modify MS risk, activity, and [...] Read more.
Background: A variety of autoimmune diseases, including MS, amplify sex-based physiological differences in immunological responsiveness. Female MS patients experience pathophysiological changes during reproductive phases (pregnancy and menopause). Sex hormones can act on immune cells, potentially enabling them to modify MS risk, activity, and progression, and to play a role in treatment. Methods: Scientific papers (published between 1998 and 2021) were selected through PubMed, Google Scholar, and Web of Science literature repositories. The search was limited to publications analyzing the hormonal profile of male and female MS patients during different life phases, in particular focusing on sex hormone treatment. Results: Both men and women with MS have lower testosterone levels compared to healthy controls. The levels of estrogens and progesterone increase during pregnancy and then rapidly decrease after delivery, possibly mediating an immune-stabilizing process. The literature examined herein evidences the neuroprotective effect of testosterone and estrogens in MS, supporting further examinations of their potential therapeutic uses. Conclusions: A correlation has been identified between sex hormones and MS clinical activity. The combination of disease-modifying therapies with estrogen or estrogen plus a progestin receptor modulator promoting myelin repair might represent an important strategy for MS treatment in the future. Full article
(This article belongs to the Special Issue Immune Dysfunction in Brain Disorders)
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18 pages, 389 KiB  
Review
Fibrinogen, Fibrinogen-like 1 and Fibrinogen-like 2 Proteins, and Their Effects
by Nurul H. Sulimai, Jason Brown and David Lominadze
Biomedicines 2022, 10(7), 1712; https://doi.org/10.3390/biomedicines10071712 - 15 Jul 2022
Cited by 13 | Viewed by 2921
Abstract
Fibrinogen (Fg) and its derivatives play a considerable role in many diseases. For example, increased levels of Fg have been found in many inflammatory diseases, such as Alzheimer’s disease, multiple sclerosis, traumatic brain injury, rheumatoid arthritis, systemic lupus erythematosus, and cancer. Although associations [...] Read more.
Fibrinogen (Fg) and its derivatives play a considerable role in many diseases. For example, increased levels of Fg have been found in many inflammatory diseases, such as Alzheimer’s disease, multiple sclerosis, traumatic brain injury, rheumatoid arthritis, systemic lupus erythematosus, and cancer. Although associations of Fg, Fg chains, and its derivatives with various diseases have been established, their specific effects and the mechanisms of actions involved are still unclear. The present review is the first attempt to discuss the role of Fg, Fg chains, its derivatives, and other members of Fg family proteins, such as Fg-like protein 1 and 2, in inflammatory diseases and their effects in immunomodulation. Full article
(This article belongs to the Special Issue Immune Dysfunction in Brain Disorders)
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