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Lipocalin-2 and MMP-9 in Alzheimer's disease

Reijntjes D. O. J. (2014) Lipocalin-2 and MMP-9 in Alzheimer's disease. Master's Thesis / Essay, Biology.

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In Alzheimer’s disease there are two hallmarks that have been described extensively in literature, the formation of amyloid-β plaques and tau neurofibrillary tangles. These two proteins are both believed to be the prime cause of Alzheimer’s disease in different hypotheses, but after decades of research, the mechanism that causes Alzheimer’s is still unknown. In the last decade or so, it has become more acknowledged that the underlying inflammation that always occurs with Alzheimer’s disease may play a crucial role, in both the development and progression of this disease. Recently two pro-inflammatory proteins were found to have detrimental effects in Alzheimer models. Both proteins cause an increase in inflammation, and cause cell death. Lipocalin-2 has been show to block a beneficial cell survival pathway mediated via PI3k/Akt, and also induce neuronal death if incubated with Aβ. MMP-9 has been shown to degrade Neuronal growth factor, NGF, which in turn leads to cell death, especially in the basal frontal cholinergic neurons. Furthermore MPP-9 may play a role in the build-up of glutamate, the aggregation of tau neurofibrillary tangles and a deregulation of the blood brain barrier. MMP-9 and Lipocalin-2 can also form a complex. The function of this complex is as of yet unknown, but it is believed to stabilize MMP-9 and therefore prolong its activity. Possibly LCN2 induces cell death when incubated with Aβ because of MMP-9 activation via formation of this MMp-9 LCN2 complex. MMP-9 is known to cleave Aβ fibrils. This might lead to the formation of Aβ neurotoxic oligomers which may explain why LCN2 induces cell death in the presence of Aβ. In conclusion these 2 proteins may play a major role in the development of Alzheimer’s disease and the possible mechanism that is suggested in this study may be a very promising research area.

Item Type: Thesis (Master's Thesis / Essay)
Degree programme: Biology
Thesis type: Master's Thesis / Essay
Language: English
Date Deposited: 15 Feb 2018 07:58
Last Modified: 15 Feb 2018 07:58

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