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Förslaget inkom 2010-07-05

Amyloid beta-peptide and synapses: Two important players in Alzheimer Disease

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Alzheimer disease (AD) is the most common form of dementia and affects millions of patients world-wide. To date, there is no cure for the disease and it’s important to learn more about the molecular mechanisms behind the disease in order to find novel therapeutic targets.
Degeneration of the synapses is one of the earliest events in AD and is closely correlated to disease progression. Despite this, the mechanisms behind the synaptic degeneration are not known. An important co-player, however, is the toxic amyloid beta-peptide (Abeta), which is produced by the sequential cleavage of the amyloid precursor protein (APP) by the beta- and gamma-secretases. We have recently identified gamma-secretase in synaptic vesicles and synaptic membranes. Now, we would like to continue with more functional studies of gamma-secretase and Abeta at the synapse. We will do this by isolating synaptic vesicles and so called synaptosomes (pinched-off nerve endings) and study beta- and gamma-secretase activity as well as effect of beta and gamma-secretase inhibitors. Within this project there are several sub-projects suitable for a 10- to 20-week thesis work.
Methods: The proposed project includes preparations of synaptosomes from rat brain, collaboration with electron microscopy facility, gamma- and beta-secretase activity assays, western blotting and measurement of reactive oxygen species and mitochondrial function.


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