Panoraia I. Siafaka
Mehmet Evren Okur
Neslihan Üstündağ Okur- 1Department of Life Sciences, School of Sciences, Program of Pharmacy, European University Cyprus, Nicosia, Cyprus
- 2Department of Pharmacology, Faculty of Pharmacy, University of Health Sciences, Istanbul, Türkiye
- 3Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Health Sciences, Istanbul, Türkiye
Editorial on the Research Topic
Innovative therapies against neurodegenerative disorders: from new active molecules to novel drug delivery systems
Introduction
Neurodegenerative disorders as Huntington's disease (HD), Alzheimer's disease (AD), Parkinson's disease (PD), Multiple Sclerosis (MS)-Pietrantonio et al. are among the greatest and rather complex disorders for modern medicine (Siafaka et al., 2021a; Siafaka et al., 2022; Siafaka et al., 2021b; Derevyanko et al., 2025). These conditions involve the progressive loss of neuronal structure and function, affecting millions globally, thus imposing heavy social, familial, and economic burdens (Van Schependom and D’haeseleer, 2023).
For years, therapeutic options for these disorders have been very limited: at present, treatments only to alleviate symptoms, and no true options for modification of the disease process are available. However, in recent years, an unprecedented innovation surge has opened new possibilities. This Research Topic “Innovative Therapies Against Neurodegenerative Disorders: from New Active Molecules to Novel Drug Delivery Systems” comprises advanced studies and opinions reflecting the current situation toward a deeper understanding and more effective treatment of neurodegenerative diseases.
From active molecules to precision medicine: redefining drug discovery
The essence of current breakthroughs is novel therapeutic agents that go beyond the conventional targets (Pietrantonio et al.). Disease-modifying therapies have started to be considered with monoclonal antibodies as aducanumab and lecanemab targeting amyloid-beta aggregates in Alzheimer’s disease. Those agents, however, are just the tip of the iceberg. Natural products (Polat et al., 2022), neurotrophic factors (Ibrahim et al., 2022), RNA-based therapies (Rabbani et al., 2025), and small-molecule modulators (McCrea et al., 2025) are all being explored, thus offering several strategies targeting diverse pathogenic mechanisms-from protein misfolding to mitochondrial dysfunction and neuroinflammation.
Advancing drug delivery systems: an advancement of delivery systems
The blood-brain barrier (BBB) is one of the most challenging and complex barriers studied in neuropharmacology; it selectively protects the brain from pathogens and molecules but prevents drug penetration. Drug delivery systems can be functionalized being able to bypass this barrier. Engineered Nanoparticles (Jia et al), and functionalized nanoparticles loaded with nucleic acids-(Edith Muolokwu et al.), liposomes, and peptide-based vectors are developed to deliver therapeutic agents straight into the central nervous system, often with targeting ability.
Non-invasive techniques like focused ultrasound (FUS), on the other hand, allow temporary and localized disruption of the BBB, allowing much greater delivery efficiency without compromising safety (Mehta et al., 2024). The vectors of gene therapy, especially those of AAV (adeno-associated viruses), are also being repurposed to carry therapeutic genes directly to brain regions affected (Abulimiti et al., 2021), offering promise for the long-term correction of genetic and proteinopathies.
Diagnostics and monitoring tools: toward early intervention
The efficient treatment demands an early and precise diagnosis; improvised techniques in imaging, fluid biomarkers (Cao et al., 2025), and nanotheranostics (Siafaka et al., 2021c) are continuously bringing into possibility the detection of neurodegenerative changes prior to the manifestation of clinical symptoms. These tools can be applied to observe the responses of treatments, furthering patient stratification, and guiding adaptive therapeutic strategies.
Future directions
The manuscripts contributed to this Research Topic have made a case for a major shift in neurodegenerative disease research—moving from reactive treatment to proactive, personalized intervention. Even so, various challenges remain; large-scale production of novel therapies, high development costs, and the examination of larger populations over longer periods of time in clinical studies.
Collaborations across disciplines such as neuroscience, pharmacology, nanotechnology, genomics, etc are necessary. Regulatory bodies should closely monitor the innovations to ensure safe and timely translation from point of discovery to patient care.
Conclusion
At present, neurodegenerative disease research is entering a transformative era. Molecules innovation, improved delivery systems, and diagnostic advances can be utilized for the management of these devastating disorders. We hope that the publications of this topic can contribute to present and future investigations for the management of neurodegenerative disorders. Scientists from various disciplines working together and continuing to innovate, can fulfill a world where the diagnosis of neurodegeneration no longer remains a death sentence but a manageable condition, and why not - a preventable one.
Author contributions
PS: Data curation, Investigation, Software, Conceptualization, Writing – review and editing, Methodology, Visualization, Validation, Resources, Project administration, Writing – original draft, Formal analysis, Funding acquisition, Supervision. MO: Data curation, Investigation, Software, Conceptualization, Writing – review and editing, Methodology, Visualization, Validation, Resources, Project administration, Writing – original draft, Formal analysis. NU: Conceptualization, Writing – review and editing, Writing – original draft, Supervision.
Funding
The author(s) declare that no financial support was received for the research and/or publication of this article.
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Generative AI statement
The author(s) declare that no Generative AI was used in the creation of this manuscript.
Publisher’s note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
References
Abulimiti, A., Lai, M. S.-L., and Chang, R. C.-C. (2021). Applications of adeno-associated virus vector-mediated gene delivery for neurodegenerative diseases and psychiatric diseases: progress, advances, and challenges. Mech. Ageing Dev. 199, 111549. doi:10.1016/j.mad.2021.111549
Cao, Y., Xu, Y., Cao, M., Chen, N., Zeng, Q., Lai, M. K. P., et al. (2025). Fluid-based biomarkers for neurodegenerative diseases. Ageing Res. Rev. 108, 102739. doi:10.1016/j.arr.2025.102739
Derevyanko, A., Tao, T., and Allen, N. J. (2025). Common alterations to astrocytes across neurodegenerative disorders. Curr. Opin. Neurobiol. 90, 102970. doi:10.1016/j.conb.2025.102970
Ibrahim, A. M., Chauhan, L., Bhardwaj, A., Sharma, A., Fayaz, F., Kumar, B., et al. (2022). Brain-derived neurotropic factor in neurodegenerative disorders. Biomedicines 10, 1143. doi:10.3390/biomedicines10051143
McCrea, L. T., Batorsky, R. E., Bowen, J. J., Yeh, H., Thanos, J. M., Fu, T., et al. (2025). Identifying brain-penetrant small-molecule modulators of human microglia using a cellular model of synaptic pruning. Neuropsychopharmacology. doi:10.1038/s41386-025-02123-1
Mehta, R. I., Ranjan, M., Haut, M. W., Carpenter, J. S., and Rezai, A. R. (2024). Focused ultrasound for neurodegenerative diseases. Magn. Reson. Imaging Clin. N. Am. 32, 681–698. doi:10.1016/j.mric.2024.03.001
Pancholi, B., Choudhary, M. K., Kumar, M., Babu, R., Vora, L. K., Khatri, D. K., et al. (2025). Cell-penetrating proteins and peptides as a promising theragnostic agent for neurodegenerative disorder. J. Drug Deliv. Sci. Technol. 107, 106816. doi:10.1016/j.jddst.2025.106816
Polat, D. Ç., Karadağ, A. E., Köprülü, R. E. P., Karantas, I. D., Mutlu, G., Çağlar, E. Ş., et al. (2022). Phytochemical compounds loaded to nanocarriers as potential therapeutic substances for alzheimer’s disease-could they be effective? Curr. Pharm. Des. 28, 2437–2460. doi:10.2174/1381612828666220411104128
Rabbani, S. A., El-Tanani, M., Sharma, S., El-Tanani, Y., Kumar, R., Saini, M., et al. (2025). RNA-Based therapies for neurodegenerative diseases targeting pathogenic proteins. Eur. J. Neurosci. 61, e70110. doi:10.1111/ejn.70110
Siafaka, P. I., Mutlu, G., and Okur, N. Ü. (2021a). Alzheimer’s disease and its related dementia types: a review on their management via nanotechnology based therapeutic strategies. Curr. Alzheimer Res. 17, 1239–1261. doi:10.2174/1567205018666210218160812
Siafaka, P. I., Okur, M. E., Erim, P. D., Çağlar, E. Ş., Özgenç, E., Gündoğdu, E., et al. (2022). Protein and gene delivery systems for neurodegenerative disorders: where do we stand today? Pharmaceutics 14, 2425. doi:10.3390/pharmaceutics14112425
Siafaka, P. I., Okur, N. Ü., Karantas, I. D., Okur, M. E., and Gündoğdu, E. A. (2021c). Current update on nanoplatforms as therapeutic and diagnostic tools: a review for the materials used as nanotheranostics and imaging modalities. Asian J. Pharm. Sci. 16, 24–46. doi:10.1016/j.ajps.2020.03.003
Siafaka, P. I., Özcan Bülbül, E., Dilsiz, P., Karantas, I. D., Okur, M. E., and Üstündağ Okur, N. (2021b). Detecting and targeting neurodegenerative disorders using electrospun nanofibrous matrices: current status and applications. J. Drug Target. 29, 476–490. doi:10.1080/1061186X.2020.1859516
Keywords: Alzheimer’s disease, neurodegenerative diseases, multiple sclerosis, nanoparticles, biomarkers, imaging
Citation: Siafaka PI, Okur ME and Üstündağ Okur N (2025) Editorial: Innovative therapies against neurodegenerative disorders: from new active molecules to novel drug delivery systems. Front. Pharmacol. 16:1640758. doi: 10.3389/fphar.2025.1640758
Received: 04 June 2025; Accepted: 06 June 2025;
Published: 25 June 2025.
Edited and reviewed by:
Barkha Yadav-Samudrala, University of North Carolina at Chapel Hill, United StatesCopyright © 2025 Siafaka, Okur and Üstündağ Okur. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Panoraia I. Siafaka, c2lhZnBhbkBnbWFpbC5jb20=