TY  - THES
AB  - Alzheimer's disease (AD) is the most frequent form of dementia, up to now only partially understood and not curable. Its importance rises with increasing life expectancy and therefore the elucidation of the molecular processes of AD becomes crucial. The A[beta]-peptide, which is produced by the amyloidogenic proteolysis of the Amyloid Precursor Protein (APP), is a main cause of the pathology by Amyloid plaque formation as well as in soluble form.
In the context of this work several proteins binding to the APP [gamma]-cleavage site are identified, including Na+-/K+-ATPase, HXK1, DNMI, MAG and 14-3-3, and a possible role concerning the [gamma]-secretase cleavage is discussed. Furthermore the already known interaction of APP and calreticulin (CRT) is characterized regarding an involvement in the production of A[beta]. The binding of the CRT-C domain to APP is not mediated by oligosaccharides and thus does not correspond to the proteins chaperone function. CRT (P domain) also interacts with Presenilin 1 (PS1), the catalytic subunit of the [gamma]-secretase. A general attendance of the protein in the process of [gamma]-cleavage remains unclear, but it seems to act substrate specific. On the one hand the secretase cleavage of APP is probably inhibited by the chaperone and on the other hand it maybe promotes the L1 proteolysis mediated by the enzyme complex. In both cases the CRT-P domain has opposite effects. According to this, CRT functions as a kind of gatekeeper and protects APP against amyloidogenic processing. The protective effect is abolished by separation of the chaperone from the cell adhesion molecule after occurrence of a yet unknown stimulus which is also the case for the exclusively PS1-binding CRT-P domain. In contrast to this, L1 is probably bound by CRT, not by CRT-P domain, and introduced to the [gamma]-secretase which cleaves the cell adhesion molecule after association of both proteins. CRT afterwards leaves the complex either alone or for stabilization of A[beta] in attendance of the peptide. Finally a comparison of the proteolytic processing of APP and L1 by different metalloproteases points out many parallels that allow conclusions concerning similarities of the particular processing and accordant etiopathology.
Consolidated, this work points out how complex and little understood the amyloidogenic APP-cleavage as well as the physiological functions of APP and its binding partners are.
DA  - 2008
KW  - , Amyloid Precursor Protein (APP) , Calretikulin (CRT) , Bindepartner , Sekretase , Alzheimer-Krankheit ,
LA  - ger
PY  - 2008
TI  - Alzheimer-Krankheit : Bindepartner und Prozessierung des Amyloid Precursor Proteins
UR  - https://nbn-resolving.org/urn:nbn:de:hbz:361-13760
Y2  - 2024-11-22T10:43:51
ER  -