Biology subjects

Dellago, H.

Publications and source records attributed to Dellago, H..

2 recordsLinked to original sources

bioRxiv2026

Iota-carrageenan protects the ocular surface from desiccation-induced cell death and tissue damage in vitro and ex vivo

Iota-carrageenan is a natural polymer with moisturizing, mucoadhesive and shear-thinning properties. In this study, we aimed to evaluate the protective effects of iota-carrageenan on ocular surface against dehydration, to demonstrate its suitability for the use in lubricant eye drops. We utilized a human epithelial corneal cell culture model to test if pre-incubation with iota-carrageenan solution could protect cells from desiccation-induced cell death, to compare its effect with other natural polymers commonly used in artificial tear products, and to determine the optimal iota-carrageenan concentration. An ex vivo porcine eye model was established to confirm the protective effect of iota-carrageenan against dehydration on ocular tissue. Pre-incubation with 1.2 mg/ml iota-carrageenan increased the survival half-life of human corneal epithelial cells upon dehydration by three-fold; the effect was in the same range as observed for large molecular weight hyaluronic acid, and superior to all other tested natural polymers. The highest tested concentration of iota- carrageenan, 1.6 mg/ml, extended the cellular survival half-life by eight-fold while maintaining healthy cellular morphology. Repeated ex vivo instillation of an iota-carrageenan-based ophthalmic formulation into porcine eyes significantly protected the ocular surface from desiccation-induced corneal damage, as shown by corneal fluorescein staining These data suggest that Iota-carrageenan effectively moisturizes and protects the ocular surface, supporting its potential as a promising novel ingredient for eye drops in the management of dry eye disease.

physiology↗

bioRxiv2019

Structural fuzziness of the RNA-organizing protein SERF1a determines a toxic gain-of-interaction

Members of the MOAG/SERF protein family have been attributed a neuropathologic significance because of their ability to enhance the proteotoxic polymerization of amyloidogenic proteins such as alpha-Synuclein (aSyn). However, the cellular function remains unknown. Here, we identify SERF1a as an RNA-organizing protein i) with no structural homology to canonical RNA-binding proteins, ii) with an RNA-chaperoning activity which favours the incorporation of RNA into nucleoli and liquid-like artificial RNA-organelles, and iii) with a high degree of conformational disorder in the RNA-bound state. We demonstrate that this type of structural fuzziness determines an undifferentiated interaction of SERF1a with aSyn and RNA. Both molecules bind to one identical, positively charged site of SERF1a by an analogous electrostatic binding mode, with similar binding affinities, and without any observable disorder-to-order transition. The absence of primary or secondary structure discriminants results in SERF1a being unable to distinguish between nucleic acid and amyloidogenic protein, leading the pro-amyloid aSyn:SERF1a interaction to prevail under conditions of cellular stress. We suggest that structural fuzziness of SERF1a accounts for an adverse gain-of-interaction which favours toxic binding to aSyn at the expense of non-toxic RNA binding, therefore promoting a functionally distorted and pathogenic process. Our results provide a direct link between structural disorder, amyloid aggregation and the malfunctioning of RNA-associated cellular processes, three hallmarks of neurodegenerative diseases.

biochemistry↗