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Neurological Disorders: Molecular Pathology and Therapeutic Approaches
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Neurological Disorders: Molecular Pathology and Therapeutic Approaches

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 20 August 2025 | Viewed by 8359

Special Issue Editor

Prof. Dr. Ana Isabel Beltrán-Velasco

E-Mail Website
Guest Editor
NBC Group, Psychology Department, School of Life and Nature Sciences, Nebrija University, 28248 Madrid, Spain
Interests: behavioral psychology; psychological testing; psychological assessment; public health; neurodegenerative disease; psychological health; pathological mechanisms and therapeutic opportunities
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Neurological disorders represent a wide range of conditions affecting the central and peripheral nervous systems. Their study is crucial because of their significant impact on public health and patient quality of life. The molecular pathology of these disorders involves complex mechanisms, including genetic mutations, protein dysfunction, oxidative stress, and neuroinflammation. These factors contribute to the neuronal degeneration and synaptic dysfunction characteristics of diseases such as Alzheimer’s, Parkinson’s, multiple sclerosis, and epilepsy.

The development of innovative therapeutic approaches has been driven by an understanding of the underlying molecular pathology. Targeted therapies, which include drugs designed to interact with specific molecules, offer the potential to modify the course of disease. Gene and cell therapies, as well as the modification of microbial profiles, are emerging as promising strategies to correct genetic defects and regenerate damaged neuronal tissue. The use of biomarkers for the early diagnosis and monitoring of disease progression has significantly improved clinical management.

Continued research in this field is essential for the development of more effective and personalized treatments. The combination of advances in molecular biology, genetics, and biotechnology promises to transform the therapeutic approach to neurological disorders.

The following topics are proposed for this SI:

  • Intracellular signalling networks in neurological disorders.
  • Identification of new therapeutic targets.
  • Genetics of neurological disorders: identification and treatment of mutations.
  • Mitochondrial diseases and neurodegeneration.
  • Gene therapy in neurological diseases: recent advances.
  • Neuroinflammation in autoimmune disorders of the central nervous system.
  • Impact of the microbiome on neurological health.

Prof. Dr. Ana Isabel Beltrán-Velasco
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

The following topics are proposed for this SI:
Intracellular signalling networks in neurological disorders.
Identification of new therapeutic targets.
Genetics of neurological disorders: identification and treatment of mutations.
Mitochondrial diseases and neurodegeneration.
Gene therapy in neurological diseases: recent advances.
Neuroinflammation in autoimmune disorders of the central nervous system.
Impact of the microbiome on neurological health.

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Published Papers (4 papers)

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20 pages, 5496 KiB  
Article
Mesenchymal Stem Cells Restore Endothelial Integrity and Alleviate Emotional Impairments in a Diabetic Mouse Model via Inhibition of MMP-9 Activity
by Aoying Chen, Yuhan Duan, Shaocong Zhou, Fangzhou Du, Huiyu Peng, Dongao Zeng, Jingwen Wang, Yue Wu, Shuaiguang Shi, Shikai Li, Shuang Yu and Jingzhong Zhang
Int. J. Mol. Sci. 2025, 26(7), 3355; https://doi.org/10.3390/ijms26073355 - 3 Apr 2025
Viewed by 381
Abstract
Diabetes mellitus (DM) has reached pandemic prevalence, significantly impacting global health. Accumulating evidence has highlighted a bidirectional relationship between diabetes and depression, with blood–brain barrier (BBB) disruption playing a pivotal role in the pathogenesis of and therapeutic approaches to both disorders. Mesenchymal stem [...] Read more.
Diabetes mellitus (DM) has reached pandemic prevalence, significantly impacting global health. Accumulating evidence has highlighted a bidirectional relationship between diabetes and depression, with blood–brain barrier (BBB) disruption playing a pivotal role in the pathogenesis of and therapeutic approaches to both disorders. Mesenchymal stem cells (MSCs) have emerged as a promising cell-based therapeutic strategy for DM; however, their potential to mitigate DM-associated emotional deficits remains unclear. This study investigates whether MSCs can restore BBB integrity and improve emotional deficits in a diabetic mouse model via matrix metalloprotein-9 (MMP-9) inhibition. We used biochemical, molecular, and behavioral analyses to assess BBB function, inflammation, and emotional behavior. Our results demonstrated that diabetic conditions induce BBB dysfunction, characterized by the MMP-9-mediated degradation of tight junction (TJ) proteins claudin-5 (Cldn5) and occludin (Ocln), alongside neuroinflammation and emotional impairments. Notably, MSC administration restored BBB integrity and attenuated neuroinflammation by suppressing MMP-9 activity and upregulating TJ proteins. Importantly, MSC treatment not only alleviated anxiety- and depressive-like behaviors but also enhanced glycemic control in DMmodels. These findings elucidate the mechanistic basis of MSC therapy for DM-related neuropsychiatric complications and, crucially, reveal its dual therapeutic efficacy in concurrently ameliorating both neuropsychiatric symptoms and metabolic dysfunction in DM models. This synergistic therapeutic effect provides a translational rationale for advancing MSC-based therapies into clinical applications. Full article
(This article belongs to the Special Issue Neurological Disorders: Molecular Pathology and Therapeutic Approaches)
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Review

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17 pages, 968 KiB  
Review
Targeting Protein Misfolding and Aggregation as a Therapeutic Perspective in Neurodegenerative Disorders
by Marta Sidoryk-Węgrzynowicz, Kamil Adamiak and Lidia Strużyńska
Int. J. Mol. Sci. 2024, 25(22), 12448; https://doi.org/10.3390/ijms252212448 - 20 Nov 2024
Cited by 1 | Viewed by 2698
Abstract
The abnormal deposition and intercellular propagation of disease-specific protein play a central role in the pathogenesis of many neurodegenerative disorders. Recent studies share the common observation that the formation of protein oligomers and subsequent pathological filaments is an essential step for the disease. [...] Read more.
The abnormal deposition and intercellular propagation of disease-specific protein play a central role in the pathogenesis of many neurodegenerative disorders. Recent studies share the common observation that the formation of protein oligomers and subsequent pathological filaments is an essential step for the disease. Synucleinopathies such as Parkinson’s disease (PD), dementia with Lewy bodies (DLB) or multiple system atrophy (MSA) are neurodegenerative diseases characterized by the aggregation of the α-synucleinprotein in neurons and/or in oligodendrocytes (glial cytoplasmic inclusions), neuronal loss, and astrogliosis. A similar mechanism of protein Tau-dependent neurodegeneration is a major feature of tauopathies, represented by Alzheimer’s disease (AD), corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), and Pick’s disease (PD). The specific inhibition of the protein misfolding and their interneuronal spreading represents a promising therapeutic strategy against both disease pathology and progression. The most recent research focuses on finding potential applications targeting the pathological forms of proteins responsible for neurodegeneration. This review highlights the mechanisms relevant to protein-dependent neurodegeneration based on the most common disorders and describes current therapeutic approaches targeting protein misfolding and aggregation. Full article
(This article belongs to the Special Issue Neurological Disorders: Molecular Pathology and Therapeutic Approaches)
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38 pages, 4137 KiB  
Review
Epigenetic Explorations of Neurological Disorders, the Identification Methods, and Therapeutic Avenues
by Zeba Firdaus and Xiaogang Li
Int. J. Mol. Sci. 2024, 25(21), 11658; https://doi.org/10.3390/ijms252111658 - 30 Oct 2024
Cited by 1 | Viewed by 1900
Abstract
Neurodegenerative disorders are major health concerns globally, especially in aging societies. The exploration of brain epigenomes, which consist of multiple forms of DNA methylation and covalent histone modifications, offers new and unanticipated perspective into the mechanisms of aging and neurodegenerative diseases. Initially, chromatin [...] Read more.
Neurodegenerative disorders are major health concerns globally, especially in aging societies. The exploration of brain epigenomes, which consist of multiple forms of DNA methylation and covalent histone modifications, offers new and unanticipated perspective into the mechanisms of aging and neurodegenerative diseases. Initially, chromatin defects in the brain were thought to be static abnormalities from early development associated with rare genetic syndromes. However, it is now evident that mutations and the dysregulation of the epigenetic machinery extend across a broader spectrum, encompassing adult-onset neurodegenerative diseases. Hence, it is crucial to develop methodologies that can enhance epigenetic research. Several approaches have been created to investigate alterations in epigenetics on a spectrum of scales—ranging from low to high—with a particular focus on detecting DNA methylation and histone modifications. This article explores the burgeoning realm of neuroepigenetics, emphasizing its role in enhancing our mechanistic comprehension of neurodegenerative disorders and elucidating the predominant techniques employed for detecting modifications in the epigenome. Additionally, we ponder the potential influence of these advancements on shaping future therapeutic approaches. Full article
(This article belongs to the Special Issue Neurological Disorders: Molecular Pathology and Therapeutic Approaches)
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27 pages, 996 KiB  
Review
The Role of Microbial Metabolites in the Progression of Neurodegenerative Diseases—Therapeutic Approaches: A Comprehensive Review
by Jorge Missiego-Beltrán and Ana Isabel Beltrán-Velasco
Int. J. Mol. Sci. 2024, 25(18), 10041; https://doi.org/10.3390/ijms251810041 - 18 Sep 2024
Cited by 3 | Viewed by 3059
Abstract
The objective of this review is to provide a comprehensive examination of the role of microbial metabolites in the progression of neurodegenerative diseases, as well as to investigate potential therapeutic interventions targeting the microbiota. A comprehensive literature search was conducted across the following [...] Read more.
The objective of this review is to provide a comprehensive examination of the role of microbial metabolites in the progression of neurodegenerative diseases, as well as to investigate potential therapeutic interventions targeting the microbiota. A comprehensive literature search was conducted across the following databases: PubMed, Scopus, Web of Science, ScienceDirect, and Wiley. Key terms related to the gut microbiota, microbial metabolites, neurodegenerative diseases, and specific metabolic products were used. The review included both preclinical and clinical research articles published between 2000 and 2024. Short-chain fatty acids have been demonstrated to play a crucial role in modulating neuroinflammation, preserving the integrity of the blood–brain barrier, and influencing neuronal plasticity and protection. Furthermore, amino acids and their derivatives have been demonstrated to exert a significant influence on CNS function. These microbial metabolites impact CNS health by regulating intestinal permeability, modulating immune responses, and directly influencing neuroinflammation and oxidative stress, which are integral to neurodegenerative diseases. Therapeutic strategies, including prebiotics, probiotics, dietary modifications, and fecal microbiota transplantation have confirmed the potential to restore microbial balance and enhance the production of neuroprotective metabolites. Furthermore, novel drug developments based on microbial metabolites present promising therapeutic avenues. The gut microbiota and its metabolites represent a promising field of research with the potential to advance our understanding of and develop treatments for neurodegenerative diseases. Full article
(This article belongs to the Special Issue Neurological Disorders: Molecular Pathology and Therapeutic Approaches)
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