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University of St. Andrews

1. Borger, Eva. New intracellular mechanisms involved in Alzheimer's disease and frontotemporal dementia .

Degree: 2012, University of St. Andrews

Dementia causes an increasing social and economic burden worldwide, demanding action regarding its diagnosis, treatment and everyday management. Recent years have seen many advances in neurodegeneration research, but the search for new truly disease modifying therapies for Alzheimer's disease (AD) and frontotemporal dementia (FTD) has so far not been successful. This is mainly due to a lack of understanding of the precise intracellular events that lead up to neuronal dysfunction in early and in late stages of the disease. This thesis describes the approaches taken to extend the current knowledge about the intracellular effects of neuronal amyloid-beta and the signalling pathways causing neuronal death or disturbed synaptic function in dementia. Endophilin-1(Ep-1), amyloid-binding alcohol dehydrogenase (ABAD), peroxiredoxin-2 (Prx-2) and the EF-hand domain family, member D2 (EFHD2) have been found to be elevated in the human brain with dementia and in mouse models for frontotemporal lobar degeneration (FTLD) or AD. The expression of these proteins as well as the expression of c-Jun N-terminal kinase (JNK), c-Jun and APP were analysed by western blotting and real-time PCR in human brains affected by AD or FTLD as well as in mouse models for AD. This provided a new insight into the regulation of these proteins in relation to each other in the ageing brain and uncovered a new potential link between elevated levels of EFHD2, Prx-2 and APP in FTLD. By studying the effects of the overexpression of Ep-1 in neurons, this research has led to a better understanding of its role in JNK-activation. It furthermore verified a protective role for Prx-2 against neurotoxicity and pointed towards a new function for Prx-2 in the regulation of JNK-signalling. The analysis of the effect of increased levels of EFHD2 uncovered for the first time its involvement in the PI3K-signalling cascade in neuronal cells. The current work has therefore contributed to the knowledge about the cellular processes that are affected by Ep-1, Prx-2 and EFHD2 in different types of dementia and will greatly benefit future research into their actions in the neuronal network. Advisors/Committee Members: Gunn-Moore, Frank J (advisor).

Subjects/Keywords: Alzheimer's disease; Frontotemporal dementia; Endophilin; Peroxiredoxin; EFHD2; C-Jun N-tmerinal kinase

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Borger, E. (2012). New intracellular mechanisms involved in Alzheimer's disease and frontotemporal dementia . (Thesis). University of St. Andrews. Retrieved from http://hdl.handle.net/10023/3092

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Borger, Eva. “New intracellular mechanisms involved in Alzheimer's disease and frontotemporal dementia .” 2012. Thesis, University of St. Andrews. Accessed April 25, 2019. http://hdl.handle.net/10023/3092.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Borger, Eva. “New intracellular mechanisms involved in Alzheimer's disease and frontotemporal dementia .” 2012. Web. 25 Apr 2019.

Vancouver:

Borger E. New intracellular mechanisms involved in Alzheimer's disease and frontotemporal dementia . [Internet] [Thesis]. University of St. Andrews; 2012. [cited 2019 Apr 25]. Available from: http://hdl.handle.net/10023/3092.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Borger E. New intracellular mechanisms involved in Alzheimer's disease and frontotemporal dementia . [Thesis]. University of St. Andrews; 2012. Available from: http://hdl.handle.net/10023/3092

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

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