Forty Years Since the Structural Elucidation of Platelet-Activating Factor (PAF): Historical, Current, and Future Research Perspectives
Abstract
:1. Platelet-Activating Factor
2. The Discovery and Structural Elucidation of the Platelet-Activating Factor
2.1. The Discovery of the Platelet-Activating Factor
2.2. Structural Elucidation of the Platelet-Activating Factor
3. The Importance of Platelet-Activating Factor Research
3.1. PAF Signalling in Physiology
3.2. PAF Signalling in Pathophysiology
4. The Potential Use of Platelet-Activating Factor Inhibitors as Therapeutics and Preventatives of Disease
4.1. PAF Inhibitors of Synthetic Origin
4.2. PAF Inhibitors of Natural Origin
5. Current Trends in Platelet-Activating Factor Research
5.1. A Potential Anti-Inflammatory Role of PAF
5.2. PAF and Cancer
5.3. Current Research Trends on PAF and PAFLL in Cardiovascular Disease
5.4. Current Research Trends on PAF in Neurological Disorders
5.5. Current Research Trends on PAF in Renal and Urinary System Disorders
6. New Frontiers in PAF Research
6.1. PAF-R Strucutral Elucidation
6.2. Induction of Inflammatory Pathways Independent of the PAF-R
7. Conclusions and Future Research Perspectives
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Title | Date | Location |
---|---|---|
1st International Symposium on Platelet-Activating Factor and Structurally Related Ether-Lipids | 26–29 June 1983 | Paris, France |
2nd International Conference on Platelet-Activating Factor and Structurally Related Ether-Lipids | 26–29 October 1986 | Gatlinburg, Tennessee, USA |
3rd International Conference on Platelet-Activating Factor and Structurally Related Ether-Lipids | 8–12 May 1989 | Tokyo, Japan |
4th International Congress on Platelet-Activating Factor and Related Lipid Mediators | 22–25 September 1992 | Snowbird, Utah, USA |
5th International Congress on Platelet-Activating Factor and Related Lipid Mediators | 12–16 September 1995 | Berlin, Germany |
6th International Congress on Platelet-Activating Factor and Related Lipid Mediators | 21–24 September 1998 | New Orleans, Louisiana, USA |
7th International Congress on Platelet-Activating Factor and Related Lipid Mediators | 24–27 September 2001 | Tokyo, Japan |
8th International Congress on Platelet-Activating Factor and Related Lipid Mediators | 6–9 October 2004 | Berlin, Germany |
6th International Conference on Phospholipase A2 and Lipid Mediators | 10–12 February 2015 | Tokyo, Japan |
PAF-R Antagonist | Target Disease or Disorder | Outcome | Reference |
---|---|---|---|
Lexipafant | Cognitive impairment complications as a result of coronary artery bypass graft | No significant reduction in cognitive impairment | [168] |
Myocardial infarction | No significant effect on streptokinase-induced hypotension in myocardial infarction patients | [169] | |
Sepsis | No significant affect in patients with severe sepsis | [170] | |
Organ failure related to pancreatitis | No significant amelioration of systemic inflammatory response syndrome in pancreatitis-induced organ failure | [171] | |
Modipafant | Asthma | No significant effect against chronic asthma | [158] |
Asthma | No significant effect in early or late responses to allergens | [172] | |
Responses to inhaled PAF | Potent inhibition of airway and neutrophil responses to PAF with a duration of up to 24 h and a reduction of secondary eicosanoid production in response to inhaled PAF | [173] | |
SR27417A SR27417A | Asthma | Modest inhibitory effects against asthma | [174,175], |
Ulcerative colitis | No evidence of efficacy in the treatment of acute ulcerative colitis | [176] | |
WEB 2086 | Asthma | No attenuation of early of late allergen-induced responses or airway hyperresponsiveness | [177] |
UVB-induced dermatitis | Significant inhibition of UVB light-induced erythema | [178] | |
BN 50730 | Rheumatoid arthritis | Ineffective in the treatment of rheumatoid arthritis | [179] |
BN 52021 | Pulmonary function in the early post ischaemic graft function in clinical lung transplantation | Improvement of alveoloarterial oxygen difference and a reduction of PAF levels | [180] |
Ro 24-238 | Psoriasis | No significant effects reported | [181] |
TCV-309 | Septic shock | No significant difference in adverse events or mortality. A substantial reduction of organ dysfunction and morbidity associated with septic shock was reported | [182] |
Levocetirizine | Chronic idiopathic urticaria | Reduction of urticarial activity score | [183] |
Rupatadine | Chronic idiopathic urticaria | Reduction of urticarial activity score but not as effective as levocetirizine | [183,184] |
Allergic rhinitis and allergies | Significant effects against both conditions as demonstrated in the comprehensive review by Mullol et al. | [185] | |
Y-24180 | Asthma | Improvement of bronchial hyperresponsiveness in patients with asthma | [186] |
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Lordan, R.; Tsoupras, A.; Zabetakis, I.; Demopoulos, C.A. Forty Years Since the Structural Elucidation of Platelet-Activating Factor (PAF): Historical, Current, and Future Research Perspectives. Molecules 2019, 24, 4414. https://doi.org/10.3390/molecules24234414
Lordan R, Tsoupras A, Zabetakis I, Demopoulos CA. Forty Years Since the Structural Elucidation of Platelet-Activating Factor (PAF): Historical, Current, and Future Research Perspectives. Molecules. 2019; 24(23):4414. https://doi.org/10.3390/molecules24234414
Chicago/Turabian StyleLordan, Ronan, Alexandros Tsoupras, Ioannis Zabetakis, and Constantinos A. Demopoulos. 2019. "Forty Years Since the Structural Elucidation of Platelet-Activating Factor (PAF): Historical, Current, and Future Research Perspectives" Molecules 24, no. 23: 4414. https://doi.org/10.3390/molecules24234414
APA StyleLordan, R., Tsoupras, A., Zabetakis, I., & Demopoulos, C. A. (2019). Forty Years Since the Structural Elucidation of Platelet-Activating Factor (PAF): Historical, Current, and Future Research Perspectives. Molecules, 24(23), 4414. https://doi.org/10.3390/molecules24234414