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New Mechanisms and Therapeutics in Neurological Diseases

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: closed (31 January 2022) | Viewed by 22372

Special Issue Editor

Special Issue Information

Dear Colleagues,

The term “neurodegenerative diseases” (NDs) collectively defines a group of pathological conditions of the nervous system characterized by the degeneration of neurons. This group of disorders includes different diseases leading to dementia or motor neuron disfunction, resulting in disability. Among them, Alzheimer’s (AD) and Parkinson’s diseases (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS) have the greatest importance because of their devastating outcomes and enormous socio-economic impact. Although they have a variegated etiology, increasing role in their pathology is ascribed to neuroinflammatory processes. Neuroinflammation may affect not only neurons but also non-neuronal astrocytes and microglia cells, as well as immune cells entering the nervous system. These cells cooperate in both the damage and the repair of diseased brain tissue. The interactions between cells and the extracellular environment have emerged as new targets for the treatment of neurodegenerative disorders. However, the heterogeneity of the molecular and cellular mechanisms underlying these diseases hinders efforts at slowing down the progression of these diseases and their effective treatment. Moreover, the availability of biomarkers with appropriate sensitivity and specificity that could predict treatment success is very limited.

Inflammatory and infectious diseases of the central nervous system (CNS) may also be involved in the pathogenesis of neurodegeneration. Microbial infection has emerged as new risk factors for NDs, and new evidence supports the universal hypothesis that some bacteria, viruses, and even fungi could be involved not only in brain inflammation but also in neurodegeneration and dementia. The diagnosis of CNS infections and the identification of potential pathogenic pathways of these diseases are also topics of interest for this Special Issue, as well as the therapy and prevention of these diseases, including vaccination.

Studies on malignant primary brain tumors are also welcome. These tumors are a highly heterogeneous group of malignancies, with varied frequency within different age groups. Among them, glioblastoma is the most common and most malignant primary CNS tumor, affecting patients of all ages, from children to adults. Glioblastoma multiforme is an especially fatal tumor type, and only moderate progress has been achieved in its clinical management in the last years.

The goal of this Special Issue is to collect original research manuscripts, short communications, and reviews on the latest advances regarding new mechanisms of and therapeutics for neurological diseases, including neurodegeneration, neuroinflammation, and tumors of the central nervous system.

Topics of interest include (but are not limited to):

  • Biological mechanisms related to neurodegeneration, inflammation, and tumorigenesis within the central nervous system;
  • Neurodegenerative diseases as proteinopathies;
  • Relationship between neurodegeneration and inflammation;
  • New potential biomarkers of Alzheimer’s disease and other neurodegenerative diseases including mild cognitive impairment, multiple sclerosis, Parkinson’s disease, Lewy body dementia, frontotemporal dementia, amyotrophic lateral sclerosis, Huntington’s disease, and prion diseases;
  • Prognostic value of biomarkers of neurodegeneration in the conversion from mild cognitive impairment to fully symptomatic dementia;
  • Cytokines, chemokines, matrix metalloproteinases as prognostic factors in carcinogenesis of CNS malignant tumors;
  • Mediators of inflammation, chemokines, and their receptors as novel tumor markers in malignant tumors of the central nervous system in relation to the histological type of tumors.
  • Relationships between coronavirus diseas 2019 (Covid-19) and neurological diseases

Prof. Dr. Barbara Mroczko
Guest Editor

Manuscript Submission Information

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Keywords

  • neurodegeneration
  • neuroinflammation
  • neurodegenerative diseases
  • neurodevelopmental disorders
  • tumor markers
  • specific proteins

Published Papers (5 papers)

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Review

34 pages, 11799 KiB  
Review
Structural Plasticity of the Hippocampus in Neurodegenerative Diseases
by Poornima D. E. Weerasinghe-Mudiyanselage, Mary Jasmin Ang, Sohi Kang, Joong-Sun Kim and Changjong Moon
Int. J. Mol. Sci. 2022, 23(6), 3349; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23063349 - 20 Mar 2022
Cited by 30 | Viewed by 5664
Abstract
Neuroplasticity is the capacity of neural networks in the brain to alter through development and rearrangement. It can be classified as structural and functional plasticity. The hippocampus is more susceptible to neuroplasticity as compared to other brain regions. Structural modifications in the hippocampus [...] Read more.
Neuroplasticity is the capacity of neural networks in the brain to alter through development and rearrangement. It can be classified as structural and functional plasticity. The hippocampus is more susceptible to neuroplasticity as compared to other brain regions. Structural modifications in the hippocampus underpin several neurodegenerative diseases that exhibit cognitive and emotional dysregulation. This article reviews the findings of several preclinical and clinical studies about the role of structural plasticity in the hippocampus in neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and multiple sclerosis. In this study, literature was surveyed using Google Scholar, PubMed, Web of Science, and Scopus, to review the mechanisms that underlie the alterations in the structural plasticity of the hippocampus in neurodegenerative diseases. This review summarizes the role of structural plasticity in the hippocampus for the etiopathogenesis of neurodegenerative diseases and identifies the current focus and gaps in knowledge about hippocampal dysfunctions. Ultimately, this information will be useful to propel future mechanistic and therapeutic research in neurodegenerative diseases. Full article
(This article belongs to the Special Issue New Mechanisms and Therapeutics in Neurological Diseases)
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29 pages, 3132 KiB  
Review
New Insights into Multiple Sclerosis Mechanisms: Lipids on the Track to Control Inflammation and Neurodegeneration
by Maria Podbielska, Joan O’Keeffe and Anna Pokryszko-Dragan
Int. J. Mol. Sci. 2021, 22(14), 7319; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22147319 - 07 Jul 2021
Cited by 24 | Viewed by 6036
Abstract
Multiple sclerosis (MS) is a central nervous system disease with complex pathogenesis, including two main processes: immune-mediated inflammatory demyelination and progressive degeneration with axonal loss. Despite recent progress in our understanding and management of MS, availability of sensitive and specific biomarkers for these [...] Read more.
Multiple sclerosis (MS) is a central nervous system disease with complex pathogenesis, including two main processes: immune-mediated inflammatory demyelination and progressive degeneration with axonal loss. Despite recent progress in our understanding and management of MS, availability of sensitive and specific biomarkers for these both processes, as well as neuroprotective therapeutic options targeted at progressive phase of disease, are still being sought. Given their abundance in the myelin sheath, lipids are believed to play a central role in underlying immunopathogenesis in MS and seem to be a promising subject of investigation in this field. On the basis of our previous research and a review of the literature, we discuss the current understanding of lipid-related mechanisms involved in active relapse, remission, and progression of MS. These insights highlight potential usefulness of lipid markers in prediction or monitoring the course of MS, particularly in its progressive stage, still insufficiently addressed. Furthermore, they raise hope for new, effective, and stage-specific treatment options, involving lipids as targets or carriers of therapeutic agents. Full article
(This article belongs to the Special Issue New Mechanisms and Therapeutics in Neurological Diseases)
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11 pages, 425 KiB  
Review
Molecular and Circulating Biomarkers of Brain Tumors
by Wojciech Jelski and Barbara Mroczko
Int. J. Mol. Sci. 2021, 22(13), 7039; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22137039 - 29 Jun 2021
Cited by 38 | Viewed by 4310
Abstract
Brain tumors are the most common malignant primary intracranial tumors of the central nervous system. They are often recognized too late for successful therapy. Minimally invasive methods are needed to establish a diagnosis or monitor the response to treatment of CNS tumors. Brain [...] Read more.
Brain tumors are the most common malignant primary intracranial tumors of the central nervous system. They are often recognized too late for successful therapy. Minimally invasive methods are needed to establish a diagnosis or monitor the response to treatment of CNS tumors. Brain tumors release molecular information into the circulation. Liquid biopsies collect and analyze tumor components in body fluids, and there is an increasing interest in the investigation of liquid biopsies as a substitute for tumor tissue. Tumor-derived biomarkers include nucleic acids, proteins, and tumor-derived extracellular vesicles that accumulate in blood or cerebrospinal fluid. In recent years, circulating tumor cells have also been identified in the blood of glioblastoma patients. In this review of the literature, the authors highlight the significance, regulation, and prevalence of molecular biomarkers such as O6-methylguanine-DNA methyltransferase, epidermal growth factor receptor, and isocitrate dehydrogenase. Herein, we critically review the available literature on plasma circulating tumor cells (CTCs), cell-free tumors (ctDNAs), circulating cell-free microRNAs (cfmiRNAs), and circulating extracellular vesicles (EVs) for the diagnosis and monitoring of brain tumor. Currently available markers have significant limitations. While much research has been conductedon these markers, there is still a significant amount that we do not yet understand, which may account for some conflicting reports in the literature. Full article
(This article belongs to the Special Issue New Mechanisms and Therapeutics in Neurological Diseases)
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33 pages, 1453 KiB  
Review
Pro- and Antiangiogenic Factors in Gliomas: Implications for Novel Therapeutic Possibilities
by Magdalena Groblewska and Barbara Mroczko
Int. J. Mol. Sci. 2021, 22(11), 6126; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22116126 - 07 Jun 2021
Cited by 11 | Viewed by 2675
Abstract
Angiogenesis, a complex, multistep process of forming new blood vessels, plays crucial role in normal development, embryogenesis, and wound healing. Malignant tumors characterized by increased proliferation also require new vasculature to provide an adequate supply of oxygen and nutrients for developing tumor. Gliomas [...] Read more.
Angiogenesis, a complex, multistep process of forming new blood vessels, plays crucial role in normal development, embryogenesis, and wound healing. Malignant tumors characterized by increased proliferation also require new vasculature to provide an adequate supply of oxygen and nutrients for developing tumor. Gliomas are among the most frequent primary tumors of the central nervous system (CNS), characterized by increased new vessel formation. The processes of neoangiogenesis, necessary for glioma development, are mediated by numerous growth factors, cytokines, chemokines and other proteins. In contrast to other solid tumors, some biological conditions, such as the blood–brain barrier and the unique interplay between immune microenvironment and tumor, represent significant challenges in glioma therapy. Therefore, the objective of the study was to present the role of various proangiogenic factors in glioma angiogenesis as well as the differences between normal and tumoral angiogenesis. Another goal was to present novel therapeutic options in oncology approaches. We performed a thorough search via the PubMed database. In this paper we describe various proangiogenic factors in glioma vasculature development. The presented paper also reviews various antiangiogenic factors necessary in maintaining equilibrium between pro- and antiangiogenic processes. Furthermore, we present some novel possibilities of antiangiogenic therapy in this type of tumors. Full article
(This article belongs to the Special Issue New Mechanisms and Therapeutics in Neurological Diseases)
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22 pages, 5156 KiB  
Review
The Implication of Reticulons (RTNs) in Neurodegenerative Diseases: From Molecular Mechanisms to Potential Diagnostic and Therapeutic Approaches
by Agnieszka Kulczyńska-Przybik, Piotr Mroczko, Maciej Dulewicz and Barbara Mroczko
Int. J. Mol. Sci. 2021, 22(9), 4630; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094630 - 28 Apr 2021
Cited by 7 | Viewed by 2783
Abstract
Reticulons (RTNs) are crucial regulatory factors in the central nervous system (CNS) as well as immune system and play pleiotropic functions. In CNS, RTNs are transmembrane proteins mediating neuroanatomical plasticity and functional recovery after central nervous system injury or diseases. Moreover, RTNs, particularly [...] Read more.
Reticulons (RTNs) are crucial regulatory factors in the central nervous system (CNS) as well as immune system and play pleiotropic functions. In CNS, RTNs are transmembrane proteins mediating neuroanatomical plasticity and functional recovery after central nervous system injury or diseases. Moreover, RTNs, particularly RTN4 and RTN3, are involved in neurodegeneration and neuroinflammation processes. The crucial role of RTNs in the development of several neurodegenerative diseases, including Alzheimer’s disease (AD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), or other neurological conditions such as brain injury or spinal cord injury, has attracted scientific interest. Reticulons, particularly RTN-4A (Nogo-A), could provide both an understanding of early pathogenesis of neurodegenerative disorders and be potential therapeutic targets which may offer effective treatment or inhibit disease progression. This review focuses on the molecular mechanisms and functions of RTNs and their potential usefulness in clinical practice as a diagnostic tool or therapeutic strategy. Full article
(This article belongs to the Special Issue New Mechanisms and Therapeutics in Neurological Diseases)
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