Part I: Analysis of the Biological Activity of Acidic Polysaccharides Extracted from Marine Organisms Sarcotragus spinosulus and Holothuria tubulosa on Tumor Cell Lines MCF-7 and MDA-MB-23 Part II: Role of LRRK2 in Parkinson's Disease: Insights into Vesicular Trafficking and Neuroinflammation

In recent years, bioactive compounds extracted from primitive marine organisms have gained attention for their potential anticancer properties. In this study, acidic polysaccharides (APs) from Holothuria tubulosa and Sarcotragus spinosulus were investigated for their effects on MDA-MB-231 and MCF-7 breast cancer cells. Holothuria-derived APs (Ht1, Ht2) exhibited anticancer potential, with Ht1 reducing cell viability and migration while promoting an epithelial-like phenotype in MDA-MB-231 cells. Ht1 also upregulated E-cadherin, while Ht2 modulated matrix metalloproteinase expression. In contrast, Sarcotragus-derived AP (Ss1) increased MCF-7 viability, downregulated E-cadherin, and upregulated Vimentin, MT1-MMP, and MMP2, indicating EMT-like changes and potential tumor-promoting effects. No effects were observed in 3D spheroids, likely due to the hydrophilic nature of APs. These findings indicate Holothuria APs as potential anticancer agents and possible pro-tumorigenic effects of Sarcotragus AP in MCF-7 cells. Pathological mutations in the LRRK2 gene are the major genetic cause of Parkinson’s disease. LRRK2 function has been linked to the control of vesicle dynamics and in the regulation of the innate immune system, but the molecular mechanisms are not fully elucidated. In this thesis we showed how exocyst complex inhibition rescues mutant LRRK2 pathogenic phenotype in cellular and drosophila models. Furthermore, prolonged exocyst inhibition leads to a reduction in the LRRK2 protein level, supporting the role of the exocyst complex in the LRRK2 pathway. Using Drosophila LRRK2 models, we were able to demonstrate a significant contribution of glial cells to the LRRK2 pathological phenotype. Furthermore, in Drosophila, neurodegeneration is associated with a significant increase in specific inflammatory peptides. Our study identifies the exocyst complex as a critical modulator of LRRK2 pathology and underscores the role of glial cells in neurodegeneration.