Sphingosine 1-phosphate receptor subtype 1 (S1P 1 ) activity in the course of Alzheimer's disease.

Autor: Martínez-Gardeazabal J; Department of Pharmacology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), B° Sarriena s/n, 48940 Leioa, Spain; Neurodegenerative Diseases, BioBizkaia Health Research Institute, Bizkaia, Spain, 48903 Barakaldo, Spain., Pereira-Castelo G; Department of Pharmacology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), B° Sarriena s/n, 48940 Leioa, Spain., Moreno-Rodríguez M; Department of Pharmacology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), B° Sarriena s/n, 48940 Leioa, Spain., Llorente-Ovejero A; Department of Pharmacology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), B° Sarriena s/n, 48940 Leioa, Spain., Fernández M; Neurodegenerative Diseases, BioBizkaia Health Research Institute, Bizkaia, Spain, 48903 Barakaldo, Spain; Department of Neurology, Hospital Universitario de Cruces, 48903 Barakaldo, Spain., Fernández-Vega I; Department of Pathology, Hospital Universitario Central de Asturias, Avda. Roma, s/n, 33011 Oviedo, Spain; Health Research Institute of Principality of Asturias (ISPA), Av. del Hospital Universitario, s/n, 33011 Oviedo, Spain., Manuel I; Department of Pharmacology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), B° Sarriena s/n, 48940 Leioa, Spain; Neurodegenerative Diseases, BioBizkaia Health Research Institute, Bizkaia, Spain, 48903 Barakaldo, Spain. Electronic address: ivan.manuel@ehu.eus., Rodríguez-Puertas R; Department of Pharmacology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), B° Sarriena s/n, 48940 Leioa, Spain; Neurodegenerative Diseases, BioBizkaia Health Research Institute, Bizkaia, Spain, 48903 Barakaldo, Spain.
Jazyk: angličtina
Zdroj: Neurobiology of disease [Neurobiol Dis] 2024 Nov; Vol. 202, pp. 106713. Date of Electronic Publication: 2024 Oct 22.
DOI: 10.1016/j.nbd.2024.106713
Abstrakt: Some specific lipid molecules in the brain act as signaling molecules, neurotransmitters, or neuromodulators, by binding to specific G protein-coupled receptors (GPCR) for neurolipids. One such receptor, sphingosine 1-phosphate receptor subtype 1 (S1P 1 ), is coupled to G i/o proteins and is involved in cell proliferation, growth, and neuroprotection. S1P 1 constitutes an interesting target for neurodegenerative diseases like multiple sclerosis and Alzheimer's disease (AD), in which changes in the sphingolipid metabolism have been observed. This study analyzes S1P 1 receptor-mediated activity in healthy brains and during AD progression using postmortem samples from controls and patients at different Braak's stages. Additionally, the distribution of S1P 1 receptor activity in human brains is compared to that in commonly used rodent models, rats and mice, through functional autoradiography, measuring [ 35 S]GTPγS binding stimulated by the S1P 1 receptor selective agonist CYM-5442 to obtain the distribution of functional activity of S1P 1 receptors. S1P 1 receptor-mediated activity, along with that of the cannabinoid CB 1 receptor, is one of the highest recorded for any GPCR in many gray matter areas of the brain, reaching maximum values in the cerebellar cortex, specific areas of the hippocampus and the basal forebrain. S1P 1 signaling is crucial in areas that regulate learning, memory, motor control, and nociception, such as the basal forebrain and basal ganglia. In AD, S1P 1 receptor activity is increased in the inner layers of the frontal cortex and underlying cortical white matter at early stages, but decreases in the hippocampus in advanced stages, indicating ongoing brain impairment. Importantly, we identified significant correlations between S1P 1 receptor activity and Braak stages, suggesting that S1P 1 receptor dysfunction is associated to disease progression, particularly in memory-related regions. The S1P signaling via S1P 1 receptor is a promising neurological target due to its role in key neurophysiological functions and its potential to modify the progression of neurodegenerative diseases. Finally, rats are suggested as a preferred experimental model for studying S1P 1 receptor-mediated responses in the human brain.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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