Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
8.1
4.9
Journals
IJMS
Special Issues
The Role of Specific Alteration in Neurological Disorders: From Molecular...
ijms-logo
Submit to Special Issue Submit Abstract to Special Issue Review for IJMS Propose a Special Issue

Journal Menu

► Journal Menu

Journal Browser

► Journal Browser
share announcement

The Role of Specific Alteration in Neurological Disorders: From Molecular Mechanisms to Therapeutic Strategies

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 April 2025 | Viewed by 12930

Special Issue Editors

Dr. Gabriele Deidda

E-Mail Website
Guest Editor
1. Queen Mary University of London, Malta Ltd., Triq L-Arcisqof Pietru Pace, VCT 2570 Victoria, Malta
2. Department of Biomedical Sciences, University of Padova, 35131 Padova, Italy
3. Padova Neuroscience Center (PNC), University of Padova, 35131 Padova, Italy
Interests: behavioral and neuropsychological testing; circuits and cellular neuroscience; cognitive and brain development; cognitive; affective and behavioral neuroscience; electrophysiology and optical imaging; focal lesions (stroke and tumors); neuro-stimulation; neuroscience methods; preclinical (animals) models; translational and clinical neuroscience
Dr. Massimo Pierucci

E-Mail Website
Guest Editor
Department of Psychology, University of Malta, Msida MSD2080, Malta
Interests: nicotine; dopamine; addiction; depression; lateral habenula
Dr. Anna Cavaccini

E-Mail Website
Guest Editor
Laboratory of Neural Circuit Assembly, Brain research Institute, University of Zurich, 8057 Zurich, Switzerland
Interests: neuromodulation; sensorimotor integration; neurodevelopment; basal ganglia; motor control

Special Issue Information

Dear Colleagues,

Neurological disorders are profoundly characterized by structural and functional alterations in neuronal and non-neuronal networks resulting from complex genetic and environmental factors during intrauterine, perinatal, and/or postnatal life periods. Several neurological disorders have been described so far in humans and reproduced in genetic and/or pharmacological animal models. Importantly, over the last few decades, it has become clear that the identification of specific dysfunctional mechanisms leading to a neurological disorder is of crucial importance and represents the first step for the design of new therapeutic strategies. Although this concept is now taken for granted, this was not always the case. A quintessential example is represented by the use of benzodiazepine over many decades (targeting ionotropic GABA-A receptors) for neurodevelopmental disorders to increase the “inhibitory” tone “assuming” that a small (developing) brain behaves in a manner that is akin to that of an adult brain. However, recent studies in different animal models of neurodevelopmental disorders have clearly shown that the polarity of GABAergic neurotransmission is altered, rendering benzodiazepine treatment ineffective or even exacerbating the pathological phenotype. Thus, experimental identification of the specific alteration (i.e., polarity of GABAergic neurotransmission) has played a pivotal role in the opening of new therapeutic perspectives for these diseases.

The latter is just an example, but it points out the general concept that this research topic embraces and aims to stress.

We welcome original research articles and reviews that shed light on or highlight molecular/cellular pathology in diverse neurological disorders and eventually identify new molecular/cellular therapeutic targets.

Dr. Gabriele Deidda
Dr. Massimo Pierucci
Dr. Anna Cavaccini
Guest Editors

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

  • neurological disorders
  • neurodevelopmental disorders
  • cellular neurophysiology
  • brain
  • molecular therapy
  • gene therapy
  • animal models
  • motor control

Benefits of Publishing in a Special Issue

  • Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
  • Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
  • Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
  • External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
  • e-Book format: Special Issues with more than 10 articles can be published as dedicated e-books, ensuring wide and rapid dissemination.

Further information on MDPI's Special Issue polices can be found here.

Published Papers (5 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review

15 pages, 1723 KiB  
Article
The Role of the Gut Microbiota in Sanfilippo Syndrome’s Physiopathology: An Approach in Two Affected Siblings
by Raquel Barbero-Herranz, María Garriga-García, Ana Moreno-Blanco, Esther Palacios, Pedro Ruiz-Sala, Saioa Vicente-Santamaría, Sinziana Stanescu, Amaya Belanger-Quintana, Guillem Pintos-Morell, Beatriz Arconada, Rosa del Campo and José Avendaño-Ortiz
Int. J. Mol. Sci. 2024, 25(16), 8856; https://doi.org/10.3390/ijms25168856 - 14 Aug 2024
Viewed by 1929
Abstract
Sanfilippo syndrome, or mucopolysaccharidosis type III (MPS III), is a rare lysosomal disease caused by congenital enzymatic deficiencies in heparan sulfate (HS) degradation, leading to organ dysfunction. The most severe hallmark of MPS III comprises neurological alterations, although gastrointestinal symptoms (GISs) have also [...] Read more.
Sanfilippo syndrome, or mucopolysaccharidosis type III (MPS III), is a rare lysosomal disease caused by congenital enzymatic deficiencies in heparan sulfate (HS) degradation, leading to organ dysfunction. The most severe hallmark of MPS III comprises neurological alterations, although gastrointestinal symptoms (GISs) have also been shown to be relevant in many patients. Here, we explored the contribution of the gut microbiota to MPS III GISs. We analyzed the composition and functionality of the gut microbiota in two MPS III siblings with the same mutation (c.544C > T, c.1080delC, in the SGSH gene) and the same diet, but with differences in their GISs, including recurrent diarrhea in one of them. Using 16S sequencing, we observed that the MPS III patients exhibited decreased alpha diversity and a lower abundance of Lachnospiraceae and Bifidobacteriaceae accompanied by a higher abundance of the Ruminococcaceae and Rikenellaceae families than the healthy control subjects. Comparing siblings, we found an increased abundance of Bacteroidaceae and a lower abundance of Ruminococcaceae and Akkermansiaceae in the GIS-free patient. This patient also had a higher relative abundance of Sus genes (SusA, SusB, SusE, and SusG) involved in glycosaminoglycan metabolism. We found higher HS levels in the stool of the two MPS III patients than in healthy volunteers, particularly in the patient with GISs. Functionally, whole fecal metabolites from the patient with GISs induced oxidative stress in vitro in healthy monocytes. Finally, the Bacteroides thetaiotaomicron strain isolated from MPS III stool samples exhibited HS degradation ability. Overall, our results reveal different microbiota compositions and functionalities in MPS III siblings, who exhibited differential gastrointestinal symptomatology. Our study may serve as a gateway to explore the impact of the gut microbiota and its potential to enhance the quality of life in Sanfilippo syndrome patients. Full article
(This article belongs to the Special Issue The Role of Specific Alteration in Neurological Disorders: From Molecular Mechanisms to Therapeutic Strategies)
►▼ Show Figures

Figure 1

32 pages, 10650 KiB  
Article
Longitudinal Neuropathological Consequences of Extracranial Radiation Therapy in Mice
by Kimberly Demos-Davies, Jessica Lawrence, Jessica Coffey, Amy Morgan, Clara Ferreira, Luke H. Hoeppner and Davis Seelig
Int. J. Mol. Sci. 2024, 25(11), 5731; https://doi.org/10.3390/ijms25115731 - 24 May 2024
Viewed by 1165
Abstract
Cancer-related cognitive impairment (CRCI) is a consequence of chemotherapy and extracranial radiation therapy (ECRT). Our prior work demonstrated gliosis in the brain following ECRT in SKH1 mice. The signals that induce gliosis were unclear. Right hindlimb skin from SKH1 mice was treated with [...] Read more.
Cancer-related cognitive impairment (CRCI) is a consequence of chemotherapy and extracranial radiation therapy (ECRT). Our prior work demonstrated gliosis in the brain following ECRT in SKH1 mice. The signals that induce gliosis were unclear. Right hindlimb skin from SKH1 mice was treated with 20 Gy or 30 Gy to induce subclinical or clinical dermatitis, respectively. Mice were euthanized at 6 h, 24 h, 5 days, 12 days, and 25 days post irradiation, and the brain, thoracic spinal cord, and skin were collected. The brains were harvested for spatial proteomics, immunohistochemistry, Nanostring nCounter® glial profiling, and neuroinflammation gene panels. The thoracic spinal cords were evaluated by immunohistochemistry. Radiation injury to the skin was evaluated by histology. The genes associated with neurotransmission, glial cell activation, innate immune signaling, cell signal transduction, and cancer were differentially expressed in the brains from mice treated with ECRT compared to the controls. Dose-dependent increases in neuroinflammatory-associated and neurodegenerative-disease-associated proteins were measured in the brains from ECRT-treated mice. Histologic changes in the ECRT-treated mice included acute dermatitis within the irradiated skin of the hindlimb and astrocyte activation within the thoracic spinal cord. Collectively, these findings highlight indirect neuronal transmission and glial cell activation in the pathogenesis of ECRT-related CRCI, providing possible signaling pathways for mitigation strategies. Full article
(This article belongs to the Special Issue The Role of Specific Alteration in Neurological Disorders: From Molecular Mechanisms to Therapeutic Strategies)
►▼ Show Figures

Figure 1

15 pages, 976 KiB  
Article
Dopamine and Norepinephrine Tissue Levels in the Developing Limbic Brain Are Impacted by the Human CHRNA6 3′-UTR Single-Nucleotide Polymorphism (rs2304297) in Rats
by Diana Carreño, Antonella Facundo, My Trang Thi Nguyen and Shahrdad Lotfipour
Int. J. Mol. Sci. 2024, 25(7), 3676; https://doi.org/10.3390/ijms25073676 - 26 Mar 2024
Cited by 2 | Viewed by 1190
Abstract
We previously demonstrated that a genetic single-nucleotide polymorphism (SNP, rs2304297) in the 3′ untranslated region (UTR) of the human CHRNA6 gene has sex- and genotype-dependent effects on nicotine-induced locomotion, anxiety, and nicotine + cue-induced reinstatement in adolescent rats. This study aims to [...] Read more.
We previously demonstrated that a genetic single-nucleotide polymorphism (SNP, rs2304297) in the 3′ untranslated region (UTR) of the human CHRNA6 gene has sex- and genotype-dependent effects on nicotine-induced locomotion, anxiety, and nicotine + cue-induced reinstatement in adolescent rats. This study aims to investigate how the CHRNA6 3′-UTR SNP influences dopaminergic and noradrenergic tissue levels in brain reward regions during baseline and after the reinstatement of drug-seeking behavior. Naïve adolescent and adult rats, along with those undergoing nicotine + cue reinstatement and carrying the CHRNA6 3′-UTR SNP, were assessed for dopamine (DA), norepinephrine (NE), and metabolites in reward pathway regions. The results reveal age-, sex-, and genotype-dependent baseline DA, NE, and DA turnover levels. Post-reinstatement, male α6GG rats show suppressed DA levels in the Nucleus Accumbens (NAc) Shell compared to the baseline, while nicotine+ cue-induced reinstatement behavior correlates with neurotransmitter levels in specific brain regions. This study emphasizes the role of CHRNA6 3′-UTR SNP in the developmental maturation of the dopaminergic and noradrenergic system in the adolescent rat brain, with tissue levels acting as predictors of nicotine + cue-induced reinstatement. Full article
(This article belongs to the Special Issue The Role of Specific Alteration in Neurological Disorders: From Molecular Mechanisms to Therapeutic Strategies)
►▼ Show Figures

Figure 1

Review

Jump to: Research

17 pages, 1057 KiB  
Review
Complexity in Genetic Epilepsies: A Comprehensive Review
by Cassandra Rastin, Laila C. Schenkel and Bekim Sadikovic
Int. J. Mol. Sci. 2023, 24(19), 14606; https://doi.org/10.3390/ijms241914606 - 27 Sep 2023
Cited by 6 | Viewed by 4506
Abstract
Epilepsy is a highly prevalent neurological disorder, affecting between 5–8 per 1000 individuals and is associated with a lifetime risk of up to 3%. In addition to high incidence, epilepsy is a highly heterogeneous disorder, with variation including, but not limited to the [...] Read more.
Epilepsy is a highly prevalent neurological disorder, affecting between 5–8 per 1000 individuals and is associated with a lifetime risk of up to 3%. In addition to high incidence, epilepsy is a highly heterogeneous disorder, with variation including, but not limited to the following: severity, age of onset, type of seizure, developmental delay, drug responsiveness, and other comorbidities. Variable phenotypes are reflected in a range of etiologies including genetic, infectious, metabolic, immune, acquired/structural (resulting from, for example, a severe head injury or stroke), or idiopathic. This review will focus specifically on epilepsies with a genetic cause, genetic testing, and biomarkers in epilepsy. Full article
(This article belongs to the Special Issue The Role of Specific Alteration in Neurological Disorders: From Molecular Mechanisms to Therapeutic Strategies)
►▼ Show Figures

Figure 1

37 pages, 1440 KiB  
Review
Evidence Synthesis of Gene Therapy and Gene Editing from Different Disorders—Implications for Individuals with Rett Syndrome: A Systematic Review
by Jatinder Singh, Ella Goodman-Vincent and Paramala Santosh
Int. J. Mol. Sci. 2023, 24(10), 9023; https://doi.org/10.3390/ijms24109023 - 19 May 2023
Cited by 2 | Viewed by 2943
Abstract
This systematic review and thematic analysis critically evaluated gene therapy trials in amyotrophic lateral sclerosis, haemoglobinopathies, immunodeficiencies, leukodystrophies, lysosomal storage disorders and retinal dystrophies and extrapolated the key clinical findings to individuals with Rett syndrome (RTT). The PRISMA guidelines were used to search [...] Read more.
This systematic review and thematic analysis critically evaluated gene therapy trials in amyotrophic lateral sclerosis, haemoglobinopathies, immunodeficiencies, leukodystrophies, lysosomal storage disorders and retinal dystrophies and extrapolated the key clinical findings to individuals with Rett syndrome (RTT). The PRISMA guidelines were used to search six databases during the last decade, followed by a thematic analysis to identify the emerging themes. Thematic analysis across the different disorders revealed four themes: (I) Therapeutic time window of gene therapy; (II) Administration and dosing strategies for gene therapy; (III) Methods of gene therapeutics and (IV) Future areas of clinical interest. Our synthesis of information has further enriched the current clinical evidence base and can assist in optimising gene therapy and gene editing studies in individuals with RTT, but it would also benefit when applied to other disorders. The findings suggest that gene therapies have better outcomes when the brain is not the primary target. Across different disorders, early intervention appears to be more critical, and targeting the pre-symptomatic stage might prevent symptom pathology. Intervention at later stages of disease progression may benefit by helping to clinically stabilise patients and preventing disease-related symptoms from worsening. If gene therapy or editing has the desired outcome, older patients would need concerted rehabilitation efforts to reverse their impairments. The timing of intervention and the administration route would be critical parameters for successful outcomes of gene therapy/editing trials in individuals with RTT. Current approaches also need to overcome the challenges of MeCP2 dosing, genotoxicity, transduction efficiencies and biodistribution. Full article
(This article belongs to the Special Issue The Role of Specific Alteration in Neurological Disorders: From Molecular Mechanisms to Therapeutic Strategies)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-5
Back to TopTop