Defective Sphingosine-1-phosphate metabolism is a druggable target in Huntington's disease

Huntington's disease is characterized by a complex and heterogeneous pathogenic profile. Studies have shown that disturbance in lipid homeostasis may represent a critical determinant in the progression of several neurodegenerative disorders. The recognition of perturbed lipid metabolism is only recently becoming evident in HD. In order to provide more insight into the nature of such a perturbation and into the effect its modulation may have in HD pathology, we investigated the metabolism of Sphingosine-1-phosphate (S1P), one of the most important bioactive lipids, in both animal models and patient samples. Here, we demonstrated that S1P metabolism is significantly disrupted in HD even at early stage of the disease and importantly, we revealed that such a dysfunction represents a common denominator among multiple disease models ranging from cells to humans through mouse models. Interestingly, the in vitro anti-apoptotic and the pro-survival actions seen after modulation of S1P-metabolizing enzymes allows this axis to emerge as a new druggable target and unfolds its promising therapeutic potential for the development of more effective and targeted interventions against this incurable condition

Ex Situ and In Situ Artificial Thermo-Aging Study of the Natural Degradation of <i>Bombyx mori</i> Silk Fibroin

This study investigates the degradation mechanism of silk fibroin through Fourier-transformed infrared spectroscopy (FTIR) analysis. The secondary structure of silk fibroin-based materials is monitored using FTIR, and various estimators are calculated to assess the impact of degradation conditions and aging time. The oxidation estimator shows consistent growth, indicating peptide bond oxidation from the early stages of artificial aging, regardless of the conditions. The environment influences the hydrolysis estimator, with water introduction leading to significant changes. The crystallinity estimator reflects the overall degradation level, affected by oxidation and hydrolysis. XRD and FTIR analysis of historical silk banners up to 500 years old demonstrate a decrease in crystallinity and an increase in hydrolysis and oxidation. The presence of water accelerates the oxidation process, while crystallinity changes are primarily driven by oxidation. Fibroin degradation affects both antiparallel and parallel regions, with water playing a crucial role in accelerating hydrolysis and causing structural shifts. This study enhances our understanding of silk fibroin degradation and provides valuable insights for preserving historical silk artifacts