The purinergic P2X7 receptor as a potential drug target to combat neuroinflammation in neurodegenerative diseases
| Autor: | Luis Gandía, Victoria Maneu, Antonio G. García, Ricardo de Pascual, María F. Cano-Abad, Iago Méndez-López, Cristina Ruiz-Ruiz, Cristóbal de los Ríos, Francesco Calzaferri, Antonio M. G. de Diego |
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| Přispěvatelé: | UAM. Departamento de Farmacología, Instituto Teófilo Hernando de I+D del Medicamento (ITH), Instituto de Investigación Sanitaria Hospital Universitario de La Paz (IdiPAZ), Universidad de Alicante. Departamento de Óptica, Farmacología y Anatomía, Neurobiología del Sistema Visual y Terapia de Enfermedades Neurodegenerativas (NEUROVIS) |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Drug
Purinergic P2X Receptor Antagonists media_common.quotation_subject Farmacología Central nervous system Disease Neuroprotection P2X7 receptors neuroinflammation Mice 03 medical and health sciences 0302 clinical medicine Neuroinflammation Alzheimer Disease P2X7 receptor antagonists Drug Discovery medicine Animals Humans neurodegenerative diseases Amyotrophic lateral sclerosis 030304 developmental biology media_common Pharmacology 0303 health sciences business.industry P2X7 receptor drugability Multiple sclerosis Purinergic receptor Neurodegenerative diseases medicine.disease Farmacia 3. Good health medicine.anatomical_structure Pharmaceutical Preparations 030220 oncology & carcinogenesis Molecular Medicine Receptors Purinergic P2X7 business Neuroscience |
| Zdroj: | Medicinal Research Reviews Biblos-e Archivo. Repositorio Institucional de la UAM instname RUA. Repositorio Institucional de la Universidad de Alicante Universidad de Alicante (UA) |
| Popis: | Neurodegenerative diseases (NDDs) represent a huge social burden, particularly in Alzheimer's disease (AD) in which all proposed treatments investigated in murine models have failed during clinical trials (CTs). Thus, novel therapeutic strategies remain crucial. Neuroinflammation is a common pathogenic feature of NDDs. As purinergic P2X7 receptors (P2X7Rs) are gatekeepers of inflammation, they could be developed as drug targets for NDDs. Herein, we review this challenging hypothesis and comment on the numerous studies that have investigated P2X7Rs, emphasizing their molecular structure and functions, as well as their role in inflammation. Then, we elaborate on research undertaken in the field of medicinal chemistry to determine potential P2X7R antagonists. Subsequently, we review the state of neuroinflammation and P2X7R expression in the brain, in animal models and patients suffering from AD, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, multiple sclerosis, and retinal degeneration. Next, we summarize the in vivo studies testing the hypothesis that by mitigating neuroinflammation, P2X7R blockers afford neuroprotection, increasing neuroplasticity and neuronal repair in animal models of NDDs. Finally, we reviewed previous and ongoing CTs investigating compounds directed toward targets associated with NDDs; we propose that CTs with P2X7R antagonists should be initiated. Despite the high expectations for putative P2X7Rs antagonists in various central nervous system diseases, the field is moving forward at a relatively slow pace, presumably due to the complexity of P2X7Rs. A better pharmacological approach to combat NDDs would be a dual strategy, combining P2X7R antagonism with drugs targeting a selective pathway in a given NDD. We would like to acknowledge the support received from the EU Horizon 2020 Research and Innovation Programme under Maria Sklodowska-Curie Grant Agreement N. 766124. We would also like to thank the support received from the Ministerio de Economía y Competitividad (MINECO, Spain; grant SAF2016-78892-R to Luis Gandía and Antonio G. García) and Fundación Teófilo Hernando |
| Databáze: | OpenAIRE |
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