Proteomic insights into the molecular mechanisms of Alzheimer’s disease using two in vitro models: neuronal cells (SH-SY5Y) and retinal photoreceptor cells (661W)

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Abstract

Amyloid β (Aβ) deposition is one of the hallmarks of Alzheimer’s disease (AD). In AD, neurons are injured by Aβ and die throughout the brain. With the disease progression, Aβ is believed to play a central role in retinal pathology. Anti-Aβ therapy has been shown to be protective and prevent cell death. However, molecular mechanisms leading to neurodegeneration underlying Aβ toxicity have not been clearly demonstrated. Better understanding of these degenerative processes is important for developing new therapy strategies for preventing cells from damage caused by AD. Our aim is to investigate the proteome changes affected by Aβ using SH-SY5Y cells which can be differentiated to a mature neuron-like phenotype, and 661W cells which show properties of both retinal ganglion and photoreceptor cells, respectively. Aβ1-42 fragments were added to cells to induce toxicity. Two concentrations (5 and 25 μm) and two time-points (6 and 24 h) were set to mimic the AD progression. A 10-plexed proteomics approach using TMT labelling was applied and carried out on a Q Exactive Orbitrap mass spectrometer followed by functional and protein-protein interaction analyses. The results of these studies, which separately identified 7525 and 5837 proteins from SH-SY5Y and 661W cells, showed that Aβ induced regulation of proteins and pathways depends on dose and time-points. The similar, yet diverse, molecular mechanisms affected by Aβ were illustrated in two different cell lines, respectively. The exploration of the direct link between Aβ and its toxicity has revealed more than ten AD-associated pathways. It is debatable whether they all equally contribute to the disease progression, however, an alternative explanation is that different mechanisms or even the same mechanism exert specific effects at different stages of AD progression. Our research generated a data resource for future investigations in human studies, which can then be used for therapeutic targeting.
Original languageEnglish
Title of host publicationProceedings of the 18th Human Proteome Organisation World Congress
Place of PublicationHouston, TX
PublisherHuman Proteome Organisation (HUPO)
Number of pages1
Publication statusPublished - 2019
EventHuman Proteome Organization World Congress (18th : 2019) - Adelaide, Australia
Duration: 15 Sep 201919 Sep 2019

Conference

ConferenceHuman Proteome Organization World Congress (18th : 2019)
Abbreviated titleHUPO 2019
CountryAustralia
CityAdelaide
Period15/09/1919/09/19

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