Identification of Autophagy as a Functional Target Suitable for the Pharmacological Treatment of Mitochondrial Membrane Protein-Associated Neurodegeneration (MPAN) In Vitro.

Mitochondrial membrane protein-associated neurodegeneration (MPAN) is a relentlessly progressive neurodegenerative disorder caused by mutations in the gene. C19orf12 has been implicated in playing a role in lipid metabolism, mitochondrial function, and autophagy, however, the precise functions remain unknown. To identify new robust cellular targets for small compound treatments, we evaluated reported mitochondrial function alterations, cellular signaling, and autophagy in a large cohort of MPAN patients and control fibroblasts.

Influence of levofloxacin and clarithromycin on the structure of DPPC monolayers.

Research on lipid/drug interactions at the nanoscale underpins the emergence of synergistic mechanisms for topical drug administration. The structural understanding of bio-mimetic systems employing 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) as a lung surfactant model mixed with antibiotics, as well as their biophysical properties, is of critical importance to modulate the effectiveness of therapeutic agents released directly to the airways. In this paper, we investigate the structural details of the interaction between Levofloxacin, 'a respiratory quinolone', and the macrolide Clarithromycin, with DPPC monolayers at the air-water interface, using a combination of Brewster angle microscopy, polarization modulation-infrared reflection-adsorption spectroscopy (PM-IRRAS), surface pressure isotherms and neutron reflectometry (NR) to describe the structural details of this interaction.

Interaction of levofloxacin with lung surfactant at the air-water interface.

The molecular-level interaction of levofloxacin with lung surfactant was investigated using Langmuir monolayers and atomistic molecular dynamics (MD) simulations. In the simulation, the DPPC/POPC mixed monolayer was used as a lung surfactant model and the molecules of levofloxacin were placed at the air-lipid interface to mimic the adsorption process on the lung surfactant model. The simulation results indicate that amphoteric levofloxacin expands the lung surfactant, also stabilizing the film for levofloxacin fractions until 10% w/w at least.