Aging and degenerative diseases : understanding neuropathology by the proteomic profiling of temporal lobe extracellular vesicles from a novel tissue-centric approach
Chew, Valerie Yi
Date of Issue2017
School of Biological Sciences
Dementia is a degenerative syndrome which results in deteriorating mental abilities. Extracellular vesicles (EVs) are vesicles important for intracellular communication and signalling although their roles in CNS still remain poorly understood. It is thought that they can facilitate the spread of neurodegenerative flow but they may also have neuroprotective roles. EVs were characterised in this work from a tissue-centric approach using a novel method called Protein Organic Solvent Precipitation (PROSPR). This method uses a low centrifugation cycle to pellet down soluble proteins and other contaminants, leaving enriched EVs behind in an organic solvent fraction. Several essential pathways were found to be disease-modified in our analyzed dementia brain tissues compared to age-matched controls. The synaptic vesicle pathway and more specifically the dopaminergic system of the temporal lobe, and the proteasome pathway were mainly found to be impaired compared to age-matched controls. Contrary, brain EVs indicated that the immune system activation pathway can be found upregulated at early events of dementia conditions. The novel findings reported in this work indicate that brain EVs play a key role in the proper function of CNS cells and that their characterization can provide novel insight on the early degenerative events that take place in dementia.
Final Year Project (FYP)
Nanyang Technological University