PPIs regulate many biological processes providing new targets for pharmacological intervention. Despite the challenges associated with the modulation of PPIs by small molecules, research efforts led to the discovery of PPIs inhibitors and some of them were approved for clinical usage. In this scenario, the research work performed during my PhD was focused on the study of two PPI interactions, α-syn aggregation and MUC1-CIN85, involved respectively in neurological disorders and cancer progression. The amyloid aggregation of α-syn plays a pivotal role in the pathogenesis of PD. To date, the therapies available for the treatment of PD are addressed to reduce the related motor symptoms; therefore, there is an increasing interest in the development of effective therapeutic agents. The inhibition of α-syn aggregation by small molecules has emerged as promising new disease-modifying strategy to slow or block the neurodegenerative process, thus offering new opportunities for drug discovery. In the last decades, several inhibitors have been reported in literature some of which are under clinical investigation. The aim of my research was to design novel α-syn aggregation inhibitors by using in silico methods. Despite extraordinary progresses have been made, the cure for most cancers is still a long way from the reality. This prompted the scientists to deeply investigate the biological pathways involved in malignancy thus allowing to identify novel targets of pharmaceutical interest. Recently, MUC1-CIN85 PPI, implicated in metastasis formation, has been validated as new target for the development of anticancer drugs. In this context, the scope of my research was the application of different structure-based approaches to gain useful structural insights for the design of MUC1-CIN85 PPI inhibitors.
|Titolo:||Study and design of modulators of protein-protein interactions implicated in tumor and neurodegenerative diseases|
|Data di pubblicazione:||27-apr-2021|
|Appare nelle tipologie:||Tesi di dottorato|