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Advances in Neurodegenerative Diseases: Research, Challenges, and Perspectives
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Advances in Neurodegenerative Diseases: Research, Challenges, and Perspectives

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: 28 February 2027 | Viewed by 5589

Editor

Dr. Constantin Ailioaie

E-Mail Website
Guest Editor
Department of Medical Physics, Alexandru Ioan Cuza University, 11 Carol I Boulevard, 700506 Iasi, Romania
Interests: photobiomodulation; pain; rehabilitation; pediatrics; nanomedicine; photo-immunotherapy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue invites original submissions on neurodegenerative diseases, with a strong focus on molecular medicine, including disease pathogenesis, molecular targets, and innovative therapeutic strategies. Neurodegenerative diseases constitute a heterogeneous group of disorders that pose major challenges to medicine and public health. The huge competition in research is generated by their complex and multifactorial etiology, incomplete understanding of molecular pathogenic mechanisms, and overlapping clinical features that often delay diagnosis and early intervention. Despite substantial financial investment over recent decades, current therapies remain largely ineffective in halting disease progression, partly due to the restrictive nature of the blood–brain barrier (BBB) and treatment-related adverse effects. Future research should leverage artificial intelligence to identify robust biomarkers for early diagnosis and to enable patient stratification through integrated analyses of genetic, clinical, and imaging data, ultimately supporting personalized therapeutic approaches. There is also a critical need for novel drugs capable of bypassing the BBB, advanced nanocarriers, and innovative nanotechnology-based platforms for reliable drug testing. Holistic and preventive strategies aimed at delaying disease onset or progression are equally important. 

We welcome original research articles, comprehensive reviews, communications, case reports, and commentaries that advance early diagnosis and management of neurodegenerative diseases.

We look forward to receiving your contributions.

Dr. Constantin Ailioaie
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 250 words) can be sent to the Editorial Office for assessment.

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-anonymized 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

  • Alzheimer’s disease
  • Parkinson’s disease
  • dementia spectrum disorders
  • pathogenic mechanisms
  • biomarkers
  • advanced imaging
  • artificial intelligence–guided diagnosis
  • nanomedicine and targeted drug delivery
  • photomedicine
  • precision medicine

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Published Papers (2 papers)

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Review

42 pages, 2506 KB  
Review
Neurodegenerative Diseases in Children: A Comprehensive Review
by Constantin Ailioaie, Laura Marinela Ailioaie, Cristinel Ionel Stan, Anca Sava and Dragos Andrei Chiran
Int. J. Mol. Sci. 2026, 27(9), 4096; https://doi.org/10.3390/ijms27094096 - 3 May 2026
Viewed by 3151
Abstract
Neurodegenerative diseases (NDDs) in children represent a heterogeneous group of rare but collectively significant disorders characterized by progressive neurological decline, developmental regression, and substantial morbidity and mortality. Unlike adult-onset neurodegeneration, pediatric conditions are predominantly genetic and frequently arise from defects in fundamental cellular [...] Read more.
Neurodegenerative diseases (NDDs) in children represent a heterogeneous group of rare but collectively significant disorders characterized by progressive neurological decline, developmental regression, and substantial morbidity and mortality. Unlike adult-onset neurodegeneration, pediatric conditions are predominantly genetic and frequently arise from defects in fundamental cellular pathways, including lysosomal degradation, mitochondrial oxidative phosphorylation, peroxisomal lipid metabolism, and myelin maintenance. This comprehensive review synthesizes current knowledge regarding the epidemiology, molecular classification, pathophysiology, and emerging therapeutic strategies of major pediatric neurodegenerative disorders. Epidemiological data indicate a “rare-but-many” landscape, where individually uncommon diseases collectively impose a measurable population burden. Mechanistically, disease progression reflects converging processes such as toxic substrate accumulation, impaired autophagy–lysosome flux, mitochondrial bioenergetic failure, oxidative stress, neuroinflammation, and glial dysfunction. Representative groups discussed include lysosomal storage disorders, leukodystrophies, mitochondrial encephalopathies, peroxisomal disorders, and other monogenic neurodegenerative syndromes. Advances in next-generation sequencing, metabolic profiling, and neuroimaging have substantially improved diagnostic accuracy and enabled earlier detection, including through newborn screening programs. Therapeutic paradigms are shifting from primarily supportive care toward mechanism-based interventions, including enzyme replacement therapy, hematopoietic stem cell transplantation, substrate reduction strategies, and gene therapy approaches. Early molecular diagnosis is increasingly recognized as critical for optimizing outcomes, particularly in disorders amenable to presymptomatic intervention. Continued integration of genomic medicine, standardized epidemiologic surveillance, and translational research will be essential to refine disease classification, improve prognostication, and expand access to targeted therapies. Collectively, pediatric neurodegenerative diseases exemplify the intersection of developmental neurobiology and inherited metabolic dysfunction, underscoring the need for multidisciplinary, precision-based clinical strategies. Full article
(This article belongs to the Special Issue Advances in Neurodegenerative Diseases: Research, Challenges, and Perspectives)
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Graphical abstract

18 pages, 866 KB  
Review
Targeted Gene and Genome-Editing Strategies for Epilepsy: Experimental Advances and Translational Challenges
by Bilal Ahmad Seh, Kashf Rafiq, Adam Legradi and Mohd Yaqub Mir
Int. J. Mol. Sci. 2026, 27(6), 2845; https://doi.org/10.3390/ijms27062845 - 20 Mar 2026
Viewed by 1862
Abstract
Epilepsy affects more than 50 million individuals worldwide, and approximately one-third of patients remain refractory to existing antiseizure medications. Advances in gene therapy and genome editing have opened new possibilities for disease-modifying interventions that directly target the molecular and circuit-level mechanisms underlying epileptogenesis. [...] Read more.
Epilepsy affects more than 50 million individuals worldwide, and approximately one-third of patients remain refractory to existing antiseizure medications. Advances in gene therapy and genome editing have opened new possibilities for disease-modifying interventions that directly target the molecular and circuit-level mechanisms underlying epileptogenesis. Recent progress in central nervous system tropic viral vectors, non-viral delivery systems, and programmable genome-editing technologies has enabled precise manipulation of neuronal and glial function in preclinical epilepsy models. Strategies range from restoration of haploinsufficient genes implicated in monogenic epilepsies, such as SCN1A in Dravet syndrome, to modulation of neuronal excitability through engineered ion channels, neuropeptides, and astrocyte-based approaches. In parallel, CRISPR-derived platforms, including transcriptional activation and repression systems, base editing, and prime editing, offer new avenues for regulating gene expression in post-mitotic neurons without introducing double-strand DNA breaks. Despite these advances, significant translational challenges remain, including efficient and cell-type-specific delivery, long-term safety, and the risk of network-level side effects in the epileptic brain. This review critically examines recent gene therapy and genome-editing approaches for epilepsy, highlights key technological and biological barriers to clinical translation, and discusses emerging strategies that may enable durable and targeted treatments for drug-resistant epilepsies. Full article
(This article belongs to the Special Issue Advances in Neurodegenerative Diseases: Research, Challenges, and Perspectives)
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