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

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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: 15 May 2024 | Viewed by 5702

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Special Issue Editors

Dr. Gabriele Deidda

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Guest Editor

Department of Biomedical Sciences, Via Ugo Bassi, University of Padova, 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

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Guest Editor

Department of Psychology, University of Malta, Msida MSD2080, Malta
Interests: nicotine; dopamine; addiction; depression; lateral habenula

Dr. Anna Cavaccini

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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

Published Papers (3 papers)

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Research

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15 pages, 976 KiB

Open AccessArticle

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

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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 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 α6^GG 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)

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Review

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17 pages, 1057 KiB

Open AccessReview

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 2 | Viewed by 2305

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 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)

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37 pages, 1440 KiB

Open AccessReview

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 1 | Viewed by 2080

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 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)

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