Inhibition of ceramide de novo synthesis by myriocin produces the double effect of reducing pathological inflammation and exerting antifungal activity against A. fumigatus airways infection

Determination of the serine palmitoyl transferase inhibitor myriocin by electrospray and Q‐trap mass spectrometry

“…with 500 µL of a solution of Avertin (10 mg/mL in saline) when the animal had to be raised from anaesthesia; for sacrifice the animal was treated with 800 µL of the same solution. One anaesthesia was reached, the animals were treated with 75 μl of Myriocin either dissolved in DMSO (1.26 μg, 3.15 nmoles) or uploaded in SLN (1.87 μg, 4.69 nmoles), by intra-trachea instilled by means of MicroSprayer® Aerosolizer -Model IA1C, attached to "FMJ-250 High Pressure Syringe" (Penn-Century Inc., US) (Caretti et al, 2014;Caretti et al, 2016). Control animals were treated with the corresponding empty vehicle.…”

“…In particular, it seems to be is a promising candidate to treat diseases such as diabetes (Ussher et al, 2011; Kurek et al, 2017) retinitis pigmentosa (Piano et al, 2013;Strettoi et al, 2010), cystic fibrosis (Caretti et al, 2014;Caretti et al, 2016) and myocardial infarction (Reforgiato et al, 2016). Myriocin is active at few nanomoles dose (1-5 microg) as a powerful immunosuppressant, and may have clinical potential in organ transplantation and for the treatment of autoimmune diseases (Fujita et al, 1994).…”

Sphingolipids from the human fungal pathogen Aspergillus fumigatus

“…At the plasma membrane level, SPLs are involved in fungal pathogenesis by regulating plasma membrane fluidity and permeability [66,67,68]. Lipid microdomains are also essential to the trafficking and to the localization of transporter such as efflux pumps that are required for multi-drug resistance [75] or in the modulation of drug-target interaction [70,71]. Plant and mammalian fungal pathogens, deficient in GlcCer, are less virulent [24,27,29,78,79].…”

“…In pulmonary chronic inflammatory diseases such as asthma or cystic fibrosis, Aspergillus infection enhances the sphingolipid de novo synthesis that leads to ceramide accumulation and mediates the inflammatory response in lung tissue. Interestingly, the serine palmitoyltransferase inhibition by myriocin has a dual anti-inflammatory and antifungal effect [70].…”

Sphingolipid metabolism in the pathophysiology and treatment of Alzheimer’s disease

“…Myriocin is a potent antibiotic derived from fungi which is used in the treatment of opportunistic infection. Interestingly, the compound shows also immunosuppressant activity [282,283].…”