Molecular determinants regulating dimerization, processing and signaling of the amyloid precursor protein
(2019)
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- Alzheimer’s disease (AD) is characterized by cognitive impairments such as apraxia, aphasia and memory decline. The two majors hallmarks of AD are neurofibrillary tangles and senile plaques. The latter are composed of amyloid peptide (Aβ) produced from its precursor, the Amyloid Precursor Protein (APP). The final cleavage of APP occurs on its C-terminal fragment (C99) by γ secretase and produces the APP intracellular domain (AICD) and Aβ. The abnormal production of Aβ leads to its aggregation and finally to its toxic effects on neurons. The work presented in this thesis focuses on the molecular determinants of APP/C99 that drive the production of both Aβ and AICD. We have shown that one particular dimeric orientation promotes strong AICD while another one favors the formation of stable oligomers composed of Aβ peptides. The characterization of these orientations could potentially aid a strategy to target AD by changing the dimerization profile leading to lower pathogenic Aβ production.
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Perrin, F. (2019). Molecular determinants regulating dimerization, processing and signaling of the amyloid precursor protein. https://hdl.handle.net/2078.5/126456