Role of extracellular vesicle and DJ-1 in intercellular communication

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Correct function of the brain requires complex, rapid, and efficient intercellular communication between varied cell types. Both neuronal and glial cells can produce extracellular vesicles (EVs) as agents of intercellular communication. EVs are heterogenous membrane-bound compartments produced through multiple pathways, resulting in different types and cargo. They are implicated in both physiological and pathological intercellular communication processes, as they can transfer nucleic acids, proteins, and lipids as well as disease-related molecules through the blood-brain barrier. Recent studies have shown their potential as biomarkers, as neuronal derived EVs were identified in biofluids such as blood, urine and cerebrospinal fluid. Within this context, DJ-1 is a particularly interesting protein: it plays a major role in oxidative stress protection, it acts as immune cell modulator and it is present in EVs. Furthermore, mutations in DJ-1 cause autosomal recessive PD and the molecular mechanisms underlying DJ-1 contribution to PD pathogenesis are still unclear.The aim of this project is to characterise and understand the role of EVs and DJ-1 in physiological and pathological intercellular communication. We will achieve this goal by answering the following questions: how does EV population change in absence of DJ-1 and what is the effect of DJ-1 cargo on recipient cells? We will employ control or DJ-1 knockout SH-SY5Y cells, as well as wild-type, PD causative and engineered DJ-1 mutants to determine the role of EVs localised DJ-1 in intercellular communication in healthy and parkinsonian cell models induced by neurotoxin or -synuclein fibril treatment. Through study by flow cytometry, RNAseq, and proteomics our results will clarify the role of DJ-1 cargo in intercellular communication and pave the way for future studies on EVs role in neurodegeneration.