Innovative Therapies for Neurodegenerative Diseases

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Gene and Cell Therapy".

Deadline for manuscript submissions: 10 May 2026 | Viewed by 457

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Department of Cellular Biology, Physiology and Immunology, Faculty of Science, University of Córdoba, 14014 Cordoba, Spain
Interests: biotechnology; biochemistry; neurodegeneration and related diseases
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Departamento de Farmacología, Farmacognosia y Botánica, Universidad Complutense de Madrid, 28040 Madrid, Spain
Interests: neurotoxicity; cognitive disorders; cancer; natural products; drug targeting strategies
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Institut de Biotecnologia i de Biomedicina (IBB), Universitat Autónoma de Barcelona, 08193 Bellaterra, Barcelona, Spain
Interests: bioactive compounds; cell signaling; drug delivery; drug discovery; enzymology; high-throughput screening; metalloproteases; molecular pharmacology; nanoparticles; neuropeptides; neurodegenerative diseases; parkinson's disease; protein-protein interaction inhibitors; protein engineering; protein structure; protease inhibitors; protein folding and aggregation; substrate specificity; X-ray crystallography
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1. LEPABE—Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal
2. ALiCE—Associate Laboratory in Chemical Engineering, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal
Interests: drug delivery; targeted therapy; brain delivery; brain cancer; glioblastoma; cancer therapy; neurodegenerative disease therapy; biophysical models; drug–membrane interactions
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Special Issue Information

Dear Colleagues,

Neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and amyotrophic lateral sclerosis (ALS) present significant medical challenges due to their irreversible progression and lack of curative treatments. In recent years, “innovative therapies” have emerged with the goal of not only alleviating symptoms but also modifying disease progression.

Neurodegenerative diseases have driven the exploration of innovative therapies, including nanotechnology, cellular therapy, gene therapy, and new pharmacological approaches. Nanotechnology enables the development of nanoparticles capable of crossing the blood-brain barrier, facilitating the direct delivery of drugs to affected neurons. Cellular and regenerative strategies involve the use of stem cells, direct and partial cellular reprogramming to restore neuronal function. Gene therapy and RNA interference have allowed for the modification of gene expression related to neurodegeneration, silencing those that contribute to the accumulation of toxic proteins in the brain. Additionally, new protein aggregation inhibitors, neuroinflammation modulators, and drugs targeting mitochondrial dysfunction have been developed to enhance energy production in neurons. These strategies represent significant advances in the fight against diseases such as Alzheimer’s and Parkinson’s, although further clinical trials are needed to validate their safety and efficacy.

The Special Issue of Pharmaceutics welcomes submissions on the following topics: pharmacological approaches, cellular therapies, nanotechnology, and neuroprotection strategies. The Special Issue of Biomedicines welcomes submissions focusing on molecular and cellular mechanisms underlying these diseases and therapeutic approaches. We invite researchers and healthcare professionals to submit their original studies or review articles with expert insights and perspectives in the field of therapeutic neuroscience.

You may choose our Joint Special Issue in Biomedicines.

Dr. Rosa María Giráldez-Pérez
Dr. María Victoria Naval
Dr. Javier Garcia-Pardo
Dr. Maria João Ramalho
Guest Editors

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Keywords

  • nanotechnology-based therapies
  • cellular and regenerative therapies
  • stem cell therapy
  • gene therapy and RNA interference
  • protein aggregation inhibitors
  • neuroinflammation modulators
  • mitochondrial dysfunction-targeted drugs
  • preclinical and clinical trials

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Published Papers (1 paper)

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Research

27 pages, 3834 KB  
Article
Neurodegeneration, Oxidative Stress, NGF/TrkA/P75NTR, and PGE2 Dysregulation Induced by PFOS Single and Repeated Treatment: Partial Protection by T3 and Other Therapeutic Approaches
by Paula Moyano, Andrea Flores, Javier Sanjuan, José Carlos Plaza, Lucía Guerra-Menéndez, María Victoria Naval, Luisa Abascal, Olga Mateo-Sierra and Javier del Pino
Pharmaceutics 2026, 18(3), 292; https://doi.org/10.3390/pharmaceutics18030292 - 27 Feb 2026
Viewed by 147
Abstract
Background/Objectives: Perfluorooctane sulfonic acid (PFOS), a persistent industrial chemical, has been associated with impairments in cognition. While several studies have attempted to identify the underlying mechanisms, the precise pathways mediating these cognitive deficits remain incompletely understood. PFOS induces cell death in basal [...] Read more.
Background/Objectives: Perfluorooctane sulfonic acid (PFOS), a persistent industrial chemical, has been associated with impairments in cognition. While several studies have attempted to identify the underlying mechanisms, the precise pathways mediating these cognitive deficits remain incompletely understood. PFOS induces cell death in basal forebrain cholinergic neurons (BFCNs), a population critically involved in maintaining cognitive function, partially through the disruption of thyroid hormone signaling. These neurotoxic effects could be mediated through multiple interconnected pathways, including the generation of oxidative stress, dysregulation of prostaglandin E2 (PGE2) signaling, and disruption of nerve growth factor (NGF) homeostasis, all of which have been independently linked to BFCN degeneration and cognitive dysfunction and reported to be induced after PFOS exposure. Methods: To systematically evaluate PFOS-induced neurodegeneration in BFCNs, we employed the SN56 cholinergic cell line derived from the basal forebrain. Cells were exposed to PFOS across a concentration range (0.1–40 μM) in combination with various pharmacological agents: triiodothyronine (T3; 15 nM), recombinant NGF (20 μM), MF-63 (1 μM), and N-acetylcysteine (1 mM). Results: Our experimental results show that PFOS exposure (both single 1-day and repeated 14-day treatments) triggers oxidative stress through reactive oxygen species accumulation coupled with diminished NRF2 pathway activity. Furthermore, PFOS disrupts both PGE2 signaling and the NGF/TrkA/P75NTR neurotrophic pathways, ultimately leading to BFCN cell death. These neurotoxic effects appear to be partially mitigated through T3 treatment, among other mechanisms. Conclusions: These findings provide valuable mechanistic insights into PFOS-induced BFCN neurodegeneration and the consequent cognitive decline while simultaneously suggesting potential therapeutic strategies to counteract these detrimental effects. Full article
(This article belongs to the Special Issue Innovative Therapies for Neurodegenerative Diseases)
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