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ADAM17 and its potential role in Alzheimer’s disease: establishing its detection through Western Blot

Pliego Caballero, Mariana (2018) ADAM17 and its potential role in Alzheimer’s disease: establishing its detection through Western Blot. Research Project 2, Biomedical Sciences.

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Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the presence of amyloid beta plaques and neurofibrillary tangles. In addition, neurodegeneration has been recognized as another important player in the development of the disease, mainly due to the release of proinflammatory factors that further promote tissue damage. Among this proinflammatory molecules, some evidence point out tumor necrosis factor-alpha (TNF-α) as a molecule with dual effects on the pathology of AD, depending if it acts as a soluble (sTNF-α) or membrane bound protein (tmTNF-α) and the receptor it binds to. While signaling through TNF Receptor 2 (TNFR2) seems to have protective effects, TNF Receptor 1(TNFR1) is mainly associated with detrimental effects. Since the tmTNF binds both TNFR1 and TNFR2, but the sTNF acts mostly through TNFR1, the ratio of sTNF-α / tmTNF-α is probably important to determine whether TNF-α participates in the pathology of Alzheimer’s disease as a protective or detrimental molecule. ADAM17 is the metalloprotease involved in the cleavage of tmTNF-α to release sTNF-α. For this reason, we aimed to test if ADAM17 protein expression is increased in the brain of a mouse model of AD, thereby promoting an increased production of sTNF-α and signaling through TNFR1, further contributing to the pathology. Since we have not studied ADAM17 before, this project was mainly focused in establishing the conditions for its proper detection through Western Blot. There were several complications to detect ADAM17 in the blots and even though we probably managed to obtain bands that correspond to our protein of interest, we were not able to differentiate the bands that correspond to its mature and immature forms.

Item Type: Thesis (Research Project 2)
Supervisor:
Supervisor nameSupervisor E mail
Eisel, U.L.M.U.L.M.Eisel@rug.nl
Degree programme: Biomedical Sciences
Thesis type: Research Project 2
Language: English
Date Deposited: 31 Aug 2018
Last Modified: 06 Sep 2018 14:21
URI: http://fse.studenttheses.ub.rug.nl/id/eprint/18490

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