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Lysosomal storage disorders (LSDs) represent a diverse group of inherited metabolic diseases in which impaired lysosomal function leads to progressive accumulation of undegraded substrates and widespread cellular dysfunction. Although traditionally classified according to the type of stored macromolecule, this substrate-based approach often fails to reflect the underlying molecular mechanisms. Recent advances in genetics and cell biology have prompted a shift toward functional classifications that group disorders by the lysosomal pathway disrupted—namely, enzymatic hydrolytic defects, transporter-related defects, biogenesis and signaling defects, and cross-organelle interaction abnormalities. This framework better captures disease complexity and provides a translational roadmap for precision medicine. The neurological system, with its high metabolic demands and vulnerability to impaired clearance mechanisms, is particularly affected, leading to clinical phenotypes ranging from developmental delay to severe neurodegeneration. Genomic technologies and multi-omics platforms have facilitated earlier diagnoses, revealed atypical variants, and informed the development of tailored therapies such as enzyme replacement, substrate reduction, chaperone-based approaches, and gene therapy. The current review proposes a cellular-pathway-oriented framework for classifying LSDs with neurological features and underscores how such an approach can assist in the development of personalized therapeutic strategies. Full article

Agro-industrial residues rich in carbohydrates represent low-cost and sustainable feedstock for enzyme production. This study demonstrates that green Arabica coffee press cake, a mannan-rich coproduct of oil extraction, is an efficient carbon source for Aspergillus niger (CFAM 1234) cultivation and for inducing mannanase production. Furthermore, the enzymes obtained were tested for mannose recovery in the enzymatic hydrolysis of healthy and defective coffee beans to investigate their hydrolytic potential. Mannanase production was investigated using various carbon sources—including ground coffee beans; coffee press cake; different particle sizes of coffee press cake; aqueous coffee cake extract (prepared at 30 g·L⁻¹ under constant stirring (300 rpm) at 80 °C for 2 h, followed by filtration.); and a commercial galactomannan, locust bean gum (LBG). CNHSO analysis was performed in the best carbon source (coffee press cake) and LBG. Statistical optimization (Plackett–Burman and Central Composite Rotatable Design) simplified the culture medium composition to coffee press cake (48.78 g·L⁻¹), yeast extract (4 g·L⁻¹), and potassium phosphate (0.25 g·L⁻¹, pH 5.5) and increased mannanases productivity to 22.4 ± 0.6 U·mL⁻¹ within only 3 days (a 42.9% improvement compared to non-optimized conditions, which were 30 g·L⁻¹, carbon source, 4 g·L⁻¹ yeast extract, 1 g·L⁻¹ Al₂O₃, 0.5 g·L⁻¹ potassium phosphate buffer (pH 5.5), 0.5 g·L⁻¹ of MgSO₄·7H₂O, and 0.05 g·L⁻¹ of CaCl₂·2H₂O, which resulted in a maximum of ~20 U·mL⁻¹ in 7 days). The crude extract also exhibited β-mannosidase activity (1.39 ± 0.06 U·mL⁻¹). When applied to the hydrolysis of untreated healthy and defective coffee beans, the enzyme preparation enabled ~25% mannose recovery (considering the value obtained through acid hydrolysis as 100%), highlighting its potential as a mannose resource. The results demonstrate that coproducts from the coffee production chain can be used as an efficient carbon source (coffee cake) for mannanase production, as well as sugar recovery (defective coffee beans), offering an integrated strategy to strengthen the circular bioeconomy and generate carbohydrates with potential industrial and nutritional applications. Full article