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Lately, APP that reaches the membrane without being severed can be internalized into endosomes in order to be proteolytically processed through two parallel pathways: an amyloidogenic pathway via acidified late endosomes and a non-amyloidogenic or anti-myloidogenic retrograde pathway via Golgi apparatus.
To date, 37 human proteins have been found to form amyloid in pathology and be associated with well-defined diseases. [2] The International Society of Amyloidosis classifies amyloid fibrils and their associated diseases based upon associated proteins (for example ATTR is the group of diseases and associated fibrils formed by TTR). [3]
The amyloidogenic processing of APP has been linked to its presence in lipid rafts. When APP molecules occupy a lipid raft region of membrane, they are more accessible to and differentially cleaved by beta secretase, whereas APP molecules outside a raft are differentially cleaved by the non-amyloidogenic alpha secretase. [ 31 ]
Additionally, endocytic trafficking of APP by BIN1 could be important because trafficking determines if APP will undergo the non-amyloidogenic or the amyloidogenic pathway. [20] For example, if APP is transported to the endosome, it will likely be cleaved by beta-secretase and undergo amyloidogenic processing, but if it accumulates on the cell ...
Thus, alpha-secretase cleavage precludes amyloid beta formation and is considered to be part of the non-amyloidogenic pathway in APP processing. Alpha secretases are members of the ADAM ('a disintegrin and metalloprotease domain') family, which are expressed on the surfaces of cells and anchored in the cell membrane .
For example, copper has been shown to 1) promote the non-amyloidogenic processing of amyloid beta precursor protein , thereby lowering amyloid beta (Aβ) production in cell culture systems [citation needed] 2) increase lifetime and decrease soluble amyloid production in APP transgenic mice, and 3) lower Aβ levels in cerebral spinal fluid in ...
In cell biology, there are a multitude of signalling pathways. Cell signalling is part of the molecular biology system that controls and coordinates the actions of cells.. Akt/PKB signalling pathway
p3 peptide is a product of non-amyloidogenic APP processing. p3 peptide is known to have a role in AD and DS , however it has not been clearly determined yet. In order to study the function of p3 peptide in AD, specific antibodies’ location techniques have been used to determine its absence or sparseness in aged non-AD brains.