Cholinergic System Neurodegeneration: Novel Pharmacotherapy

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Drug Discovery, Development and Delivery".

Deadline for manuscript submissions: 31 July 2025 | Viewed by 6171

Special Issue Editors


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Guest Editor
Departamento de Farmacología y Toxicología, Universidad Complutense de Madrid, 28040 Madrid, Spain
Interests: basal forebrain cholinergic neurons; neurotoxicity; environmental pollutants; cognitive disorders

E-Mail Website
Guest Editor
Departamento de Farmacología y Toxicología, Universidad Complutense de Madrid, 28040 Madrid, Spain
Interests: basal forebrain cholinergic neurons; neurotoxicity, environmental pollutans; cognitive disorders

Special Issue Information

Dear Colleagues,

This Special Issue, entitled “Cholinergic System Neurodegeneration: Novel therapies”, will mainly focus on the molecular, structural, neurochemical, pathological, and behavioral studies of the cholinergic system’s neurodegeneration, its impact on disease, and novel therapies used to avoid them.

Acetylcholine was the first neurotransmitter identified by the studies of Henry Dale and Otto Loewi in 1936, which discovered chemical neurotransmission and afterwards the complex regulation of the cholinergic system and its functions. Cholinergic transmission regulates many functions peripherally (cardiovascular, gastrointestinal, respiratory, and reproductive systems, among others) and on the central nervous system (affective, memory, learning, and sleep regulation, among others), and its disruption is involved in different harmful neuropathologies.

As Guest Editor, I would be very pleased if you contributed to this Special Issue with either an original research paper or a focused review with emphasis on cholinergic system neurodegeneration and potential therapeutic approaches.

Prof. Dr. Javier del Pino
Dr. Paula Moyano
Guest Editors

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Keywords

  • cholinergic system
  • neurodegeneration
  • acetylcholine
  • cholinergic neurons
  • cholinergic pathologies
  • therapeutic approaches

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Published Papers (1 paper)

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Research

23 pages, 15837 KiB  
Article
Thyroid Hormone Neuroprotection Against Perfluorooctane Sulfonic Acid Cholinergic and Glutamatergic Disruption and Neurodegeneration Induction
by Paula Moyano, Gabriela Guzmán, Andrea Flores, Jimena García, Lucia Guerra-Menéndez, Javier Sanjuan, José Carlos Plaza, Luisa Abascal, Olga Mateo and Javier Del Pino
Biomedicines 2024, 12(11), 2441; https://doi.org/10.3390/biomedicines12112441 - 24 Oct 2024
Viewed by 5634
Abstract
Background: Perfluorooctane sulfonic acid (PFOS), a widely used industrial chemical, was reported to induce memory and learning process dysfunction. Some studies tried to reveal the mechanisms that mediate these effects, but how they are produced is still unknown. Basal forebrain cholinergic neurons [...] Read more.
Background: Perfluorooctane sulfonic acid (PFOS), a widely used industrial chemical, was reported to induce memory and learning process dysfunction. Some studies tried to reveal the mechanisms that mediate these effects, but how they are produced is still unknown. Basal forebrain cholinergic neurons (BFCN) maintain cognitive function and their selective neurodegeneration induces cognitive decline, as observed in Alzheimer’s disease. PFOS was reported to disrupt cholinergic and glutamatergic transmissions and thyroid hormone action, which regulate cognitive processes and maintain BFCN viability. Objective/Methods: To evaluate PFOS neurodegenerative effects on BFCN and the mechanisms that mediate them, SN56 cells (a neuroblastoma cholinergic cell line from the basal forebrain) were treated with PFOS (0.1 µM to 40 µM) with or without thyroxine (T3; 15 nM), MK-801 (20 µM) or acetylcholine (ACh; 10 µM). Results: In the present study, we found that PFOS treatment (1 or 14 days) decreased thyroid receptor α (TRα) activity by decreasing its protein levels and increased T3 metabolism through increased deiodinase 3 (D3) levels. Further, we observed that PFOS treatment disrupted cholinergic transmission by decreasing ACh content through decreased choline acetyltransferase (ChAT) activity and protein levels and through decreasing muscarinic receptor 1 (M1R) binding and protein levels. PFOS also disrupted glutamatergic transmission by decreasing glutamate content through increased glutaminase activity and protein levels and through decreasing N-methyl-D-aspartate receptor subunit 1 (NMDAR1); effects mediated through M1R disruption. All these effects were mediated through decreased T3 activity and T3 supplementation partially restored to the normal state. Conclusions: These findings may assist in understanding how PFOS induces neurodegeneration, and the mechanisms involved, especially in BFCN, to explain the process that could lead to cognitive dysfunction and provide new therapeutic tools to treat and prevent its neurotoxic effects. Full article
(This article belongs to the Special Issue Cholinergic System Neurodegeneration: Novel Pharmacotherapy)
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