It appears that the immunocytochemical methods applied in this and other studies [ 11– 17, 17, 22, 39] do not monitor the neuronal secretory pathway of APP processing leading to normal secretion of Aβ1 40 and Aβ1 42.
It possesses a BRICHOS domain, a conserved motif common to members of the BRI, ChM-I, SP-C and CA11 protein families, thought to have a role in the targeting of the respective proteins to the secretory pathway or to intracellular processing [10].
ER is the first compartment of the secretory pathway and is a processing station for secreted and transmembrane proteins.
After processing by the secretory pathway, the signal sequence and glycosylphosphatidylinositol (GPI) targeting sequence are cleaved, and the somatostatin sequence, with a free N-terminus is displayed on the plasma membrane by GPI covalently linked to the C-terminus.
The protein secretory pathway is an extensive process in eukaryal cells, as it is responsible for processing approximately one-third of all proteins.
Changes in the extracellular environment of a cell can adversely affect the normal homeostasis of the endoplasmic reticulum (ER), which disrupts the folding and processing of secretory pathway proteins.
Neurons have a unique organization of their secretory pathway, with membrane and lipid processing in somatic Golgi, and additional ER-to-Golgi transport in dendrites [41], which enables dendrites with Golgi to be longer and more complex [42].
This indicates complete processing of the fusion proteins by cleavage within the furS recognition site in the secretory pathway, resulting in secretion of processed GrB and both fusion partners GST and MBP.
α1-PDX was initially showed to be a potent inhibitor of various substrates cleavage by Furin in different species and subsequently demonstrated to also inhibit all PCs involved in processing within the constitutive secretory pathway [9] [12].
The endoplasmic reticulum (ER) is responsible for folding and processing proteins entering the secretory pathway.
Blocking or decrease of processing in the secretory pathway is a hallmark of ER stress [5].
