P2X7-pannexin-1 and amyloid β-induced oxysterol input in human retinal cell: Role in age-related macular degeneration?

Olivier, Elodie; Dutot, Mélody; Regazzetti, Anne; Léguillier, Teddy; Dargère, Delphine; Auzeil, Nicolas; Laprévôte, Olivier; Rat, Patrice

doi:10.1016/j.biochi.2016.04.014

Cited by 44 publications

(44 citation statements)

References 50 publications

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“…The roles of P2Y 2 and P2X7R in corneal wound healing have been reviewed ( Minns and Trinkaus-Randall, 2016 ; Minns et al, 2016 ). P2X7R activation in oxysterol cytotoxicity may be a target for the treatment of age-related macular degeneration ( Olivier et al, 2016 ).…”

Section: Diseases Of the Special Sensesmentioning

confidence: 99%

Purinergic Signalling: Therapeutic Developments

2017

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Purinergic signalling, i.e., the role of nucleotides as extracellular signalling molecules, was proposed in 1972. However, this concept was not well accepted until the early 1990’s when receptor subtypes for purines and pyrimidines were cloned and characterised, which includes four subtypes of the P1 (adenosine) receptor, seven subtypes of P2X ion channel receptors and 8 subtypes of the P2Y G protein-coupled receptor. Early studies were largely concerned with the physiology, pharmacology and biochemistry of purinergic signalling. More recently, the focus has been on the pathophysiology and therapeutic potential. There was early recognition of the use of P1 receptor agonists for the treatment of supraventricular tachycardia and A2A receptor antagonists are promising for the treatment of Parkinson’s disease. Clopidogrel, a P2Y12 antagonist, is widely used for the treatment of thrombosis and stroke, blocking P2Y12 receptor-mediated platelet aggregation. Diquafosol, a long acting P2Y2 receptor agonist, is being used for the treatment of dry eye. P2X3 receptor antagonists have been developed that are orally bioavailable and stable in vivo and are currently in clinical trials for the treatment of chronic cough, bladder incontinence, visceral pain and hypertension. Antagonists to P2X7 receptors are being investigated for the treatment of inflammatory disorders, including neurodegenerative diseases. Other investigations are in progress for the use of purinergic agents for the treatment of osteoporosis, myocardial infarction, irritable bowel syndrome, epilepsy, atherosclerosis, depression, autism, diabetes, and cancer.

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Section: Diseases Of the Special Sensesmentioning

confidence: 99%

Purinergic Signalling: Therapeutic Developments

2017

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“…SA could significantly counteract the inflammatory and cytotoxic responses caused by 7-ketocholesterol (7KCh), both in vivo and in vitro. 7KCh is an oxysterol that has been related to several degenerative diseases, including AMD [57,58,108], atherosclerosis [109][110][111][112], Parkinson´s [113], and Alzheimer´s disease [114][115][116]. A low concentrations of SA has been shown to protect ARPE-19 cells from 7KCh-induced cell death, as well as lessen the expression of several inflammatory cytokines, such as IL-1β, IL-6, IL-8 and vascular endothelial growth factor (VEGF) [117][118][119].…”

Section: Sa and Therapeutic Opportunitiesmentioning

confidence: 99%

Sterculic Acid: The Mechanisms of Action beyond Stearoyl-CoA Desaturase Inhibition and Therapeutic Opportunities in Human Diseases

Peláez

Pariente

Pérez-Sala

et al. 2020

Cells

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In many tissues, stearoyl-CoA desaturase 1 (SCD1) catalyzes the biosynthesis of monounsaturated fatty acids (MUFAS), (i.e., palmitoleate and oleate) from their saturated fatty acid (SFA) precursors (i.e., palmitate and stearate), influencing cellular membrane physiology and signaling, leading to broad effects on human physiology. In addition to its predominant role in lipid metabolism and body weight control, SCD1 has emerged recently as a potential new target for the treatment for various diseases, such as nonalcoholic steatohepatitis, Alzheimer’s disease, cancer, and skin disorders. Sterculic acid (SA) is a cyclopropene fatty acid originally found in the seeds of the plant Sterculia foetida with numerous biological activities. On the one hand, its ability to inhibit stearoyl-CoA desaturase (SCD) allows its use as a coadjuvant of several pathologies where this enzyme has been associated. On the other hand, additional effects independently of its SCD inhibitory properties, involve anti-inflammatory and protective roles in retinal diseases such as age-related macular degeneration (AMD). This review aims to summarize the mechanisms by which SA exerts its actions and to highlight the emerging areas where this natural compound may be of help for the development of new therapies for human diseases.

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“…What factors can contribute to such activation and synergistically sensitize neurons to death in the retina? A number of stressors and danger factors capable of activating the Panx1 channel are known to be present and/or increased in the retina upon challenge with IOP elevation, including: i) mechanical stress from the increased IOP 2 ; ii) eATP, acting through purinergic P2X receptors 3 ; iii) caspases 3/7, which irreversibly activate Panx1 by proteolytic cleavage 55 ; iv) ischemic injury 7 , 49 , 56 ; v) extracellular glutamate, which activates Panx1 via the NMDA receptor/Src kinase pathway 9 ; and vi) other danger factors, such as high levels of extracellular K + , Zn2 + or β-amyloid 57 – 59 . In the current study, we examined the toxic effect of a combination of ischemia and ATP and utilized N2a cells engineered to over-express Panx1.…”

Section: Discussionmentioning

confidence: 99%

Pannexin 1 sustains the electrophysiological responsiveness of retinal ganglion cells

Dvoriantchikova

Pronin

Kurtenbach

et al. 2018

Sci Rep

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Pannexin 1 (Panx1) forms ATP-permeable membrane channels that play a key role in purinergic signaling in the nervous system in both normal and pathological conditions. In the retina, particularly high levels of Panx1 are found in retinal ganglion cells (RGCs), but the normal physiological function in these cells remains unclear. In this study, we used patch clamp recordings in the intact inner retina to show that evoked currents characteristic of Panx1 channel activity were detected only in RGCs, particularly in the OFF-type cells. The analysis of pattern electroretinogram (PERG) recordings indicated that Panx1 contributes to the electrical output of the retina. Consistently, PERG amplitudes were significantly impaired in the eyes with targeted ablation of the Panx1 gene in RGCs. Under ocular hypertension and ischemic conditions, however, high Panx1 activity permeated cell membranes and facilitated the selective loss of RGCs or stably transfected Neuro2A cells. Our results show that high expression of the Panx1 channel in RGCs is essential for visual function in the inner retina but makes these cells highly sensitive to mechanical and ischemic stresses. These findings are relevant to the pathophysiology of retinal disorders induced by increased intraocular pressure, such as glaucoma.

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P2X7-pannexin-1 and amyloid β-induced oxysterol input in human retinal cell: Role in age-related macular degeneration?

Cited by 44 publications

References 50 publications

Purinergic Signalling: Therapeutic Developments

Purinergic Signalling: Therapeutic Developments

Sterculic Acid: The Mechanisms of Action beyond Stearoyl-CoA Desaturase Inhibition and Therapeutic Opportunities in Human Diseases

Pannexin 1 sustains the electrophysiological responsiveness of retinal ganglion cells

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