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Lipocalin-2 as therapeutic target for Alzheimer’s disease: Effect of Deferiprone in the cognition of J20 mice

López Vázquez, María (2019) Lipocalin-2 as therapeutic target for Alzheimer’s disease: Effect of Deferiprone in the cognition of J20 mice. Master's Research Project 1, Biomedical Sciences.

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Abstract

Lipocalin-2 (Lcn-2), an acute phase protein associated with iron homeostasis, has been reported to be involved in various neurodegenerative conditions, including Alzheimer's Disease (AD). For instance, recent studies suggest that this protein, which is overexpressed in AD, may play a role in neuroinflammation and iron dysregulation, two hallmarks of the neuropathology of this disorder. Additionally, iron has been found to induce the up-regulation of Lcn-2. Here, we use the iron chelator Deferiprone to target Lcn-2. The main hypothesis is that Deferiprone might reduce iron accumulation in the brain of J20 mouse model of AD and, subsequently, prevent the up-regulation of the protein. For this, wild-type (WT) and J20 mice were given either Deferiprone (50 mg/kg) or water daily during 12 weeks. Concretely, this report will focus on the cognitive aspects, which were tested over a series of behavioural tasks that started after 5 weeks of treatment. While there are genotype differences between WT and J20 mice, the administration of Deferiprone did not improve the cognitive performance of the J20 mice. Since iron chelation therapies has shown encouraging results in the context of cognitive impairments in AD in the past, further research is needed to explain why in our study Deferiprone could not ameliorate the memory impairment in the J20 mice. At the same time, the neuropathological analysis of the brains might help to clarify the results obtained here, especially the stainings for iron and Lcn-2. Finally, although this study could not validate Lcn-2 as a therapeutic target, the role and relevance of this protein in AD should be studied more comprehensively.

Item Type: Thesis (Master's Research Project 1)
Supervisor name: Eisel, U.L.M.
Degree programme: Biomedical Sciences
Thesis type: Master's Research Project 1
Language: English
Date Deposited: 14 Oct 2019
Last Modified: 14 Oct 2019 11:46
URI: https://fse.studenttheses.ub.rug.nl/id/eprint/21103

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