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From Molecules to Medicines: Exploring Neurodegenerative Pathways for Targeted Neuropharmacology

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: 20 July 2025 | Viewed by 2791

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Department of Experimental and Clinical Pharmacology, Centre for Preclinical Research (CBP), The Medical University of Warsaw, Banacha 1B St., 02-097 Warsaw, Poland
Interests: Parkinson’s disease; therapy; drug; repurposing; novel compound; neurodegeneration; neuroinflammation
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Special Issue Information

Dear Colleagues,

Neurological diseases affect a significant portion of the global population, contributing to significant morbidity and mortality. This Special Issue aims to delve into the intricate landscape of neurodegenerative pathology, shedding light on key elements such as endothelial dysfunction, blood–brain barrier (BBB) damage, oxidative stress, inflammation, coagulation pathway dysfunction, and neuronal and glial degeneration. This focus extends to the multifaceted challenges of drug development in neuropharmacology, spanning effective blood–brain barrier penetration, optimization of drug delivery systems, and the revolutionary impact of biomarkers in personalized neuropharmacology. As we navigate the complexities of the human brain and its signaling pathways, the goal is to foster breakthroughs that modify disease progression, enhance long-term survival, and elevate the quality of life for individuals affected by neurological diseases. Researchers are invited to contribute original articles and reviews across diverse research areas, including disease modeling, drug studies, and therapeutic interventions, in order to collectively advance our understanding and pave the way for innovative pharmacological interventions in neuropharmacology.

This Special Issue is supervised by Dr. Malgorzata Zaremba and assisted by our Topical Advisory Panel Member Dr. Suman Chowdhury (Department of Pharmacology, Physiology, Neuroscience NJMS, Rutgers University Newark-07103, New Jersey, USA).

Dr. Malgorzata Zaremba
Guest Editor

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Keywords

  • disease modeling
  • drug studies
  • therapeutic interventions
  • neuropharmacology
  • innovative pharmacological interventions

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Published Papers (2 papers)

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15 pages, 29548 KiB  
Article
A Comparative Study of a Potent CNS-Permeable RARβ-Modulator, Ellorarxine, in Neurons, Glia and Microglia Cells In Vitro
by Yunxi Zhang, Lilie Gailloud, Alexander Shin, Jessica Fewkes, Rosella Pinckney, Andrew Whiting and Paul Chazot
Int. J. Mol. Sci. 2025, 26(8), 3551; https://doi.org/10.3390/ijms26083551 - 10 Apr 2025
Viewed by 460
Abstract
Vitamin A (retinol) and its derivatives (retinoids) assume critical roles in neural development, cellular differentiation, axon elongation, programmed cell apoptosis and various fundamental cellular processes. Retinoids function by binding to specific nuclear receptors, such as retinoic acid receptors (RARs) and retinoid X receptors [...] Read more.
Vitamin A (retinol) and its derivatives (retinoids) assume critical roles in neural development, cellular differentiation, axon elongation, programmed cell apoptosis and various fundamental cellular processes. Retinoids function by binding to specific nuclear receptors, such as retinoic acid receptors (RARs) and retinoid X receptors (RXRs), activating specific signalling pathways in the cells. The disruption of the retinoic acid signalling pathway can result in neuroinflammation, oxidative and ER stress and mitochondrial dysfunction and has been implicated in a wide range of neurodegenerative diseases. The present study explored the potential therapeutic application of our innovative CNS-permeable synthetic retinoid, Ellorarxine, for the treatment of neurodegenerative disorders in vitro. An MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) tetrazolium assay, lactate dehydrogenase (LDH) assay, enzyme-linked immunosorbent assay (ELISA), immunocytochemistry and immunofluorescence staining were performed. Ellorarxine increased Cyp26 and, selectively, RARβ protein expression in neurons, glia and microglia. Ellorarxine significantly reduced cell death (neurons, glia), increased mitochondrial viability (neurons), modulated cytokine release (microglia), and positively regulated cellular autophagy (neurons, glia, microglia). These results suggest that Ellorarxine is a promising drug candidate that should be further investigated in the treatment of neurodegenerative diseases. Full article
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23 pages, 2473 KiB  
Article
Head-to-Head Comparison of Aptamer- and Antibody-Based Proteomic Platforms in Human Cerebrospinal Fluid Samples from a Real-World Memory Clinic Cohort
by Raquel Puerta, Amanda Cano, Pablo García-González, Fernando García-Gutiérrez, Maria Capdevila, Itziar de Rojas, Clàudia Olivé, Josep Blázquez-Folch, Oscar Sotolongo-Grau, Andrea Miguel, Laura Montrreal, Pamela Martino-Adami, Asif Khan, Adelina Orellana, Yun Ju Sung, Ruth Frikke-Schmidt, Natalie Marchant, Jean Charles Lambert, Maitée Rosende-Roca, Montserrat Alegret, Maria Victoria Fernández, Marta Marquié, Sergi Valero, Lluís Tárraga, Carlos Cruchaga, Alfredo Ramírez, Mercè Boada, Bart Smets, Alfredo Cabrera-Socorro and Agustín Ruizadd Show full author list remove Hide full author list
Int. J. Mol. Sci. 2025, 26(1), 286; https://doi.org/10.3390/ijms26010286 - 31 Dec 2024
Cited by 2 | Viewed by 1751
Abstract
High-throughput proteomic platforms are crucial to identify novel Alzheimer’s disease (AD) biomarkers and pathways. In this study, we evaluated the reproducibility and reliability of aptamer-based (SomaScan® 7k) and antibody-based (Olink® Explore 3k) proteomic platforms in cerebrospinal fluid (CSF) samples from the [...] Read more.
High-throughput proteomic platforms are crucial to identify novel Alzheimer’s disease (AD) biomarkers and pathways. In this study, we evaluated the reproducibility and reliability of aptamer-based (SomaScan® 7k) and antibody-based (Olink® Explore 3k) proteomic platforms in cerebrospinal fluid (CSF) samples from the Ace Alzheimer Center Barcelona real-world cohort. Intra- and inter-platform reproducibility were evaluated through correlations between two independent SomaScan® assays analyzing the same samples, and between SomaScan® and Olink® results. Association analyses were performed between proteomic measures, CSF biological traits, sample demographics, and AD endophenotypes. Our 12-category metric of reproducibility combining correlation analyses identified 2428 highly reproducible SomaScan CSF measures, with over 600 proteins well reproduced on another proteomic platform. The association analyses among AD clinical phenotypes revealed that the significant associations mainly involved reproducible proteins. The validation of reproducibility in these novel proteomics platforms, measured using this scarce biomaterial, is essential for accurate analysis and proper interpretation of innovative results. This classification metric could enhance confidence in multiplexed proteomic platforms and improve the design of future panels. Full article
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