Open AccessSecretory Sorting Receptors Carboxypeptidase E and Secretogranin III in Amyloid β‐Associated Neural Degeneration in A lzheimer's Disease
Author(s) -
Plá Virginia,
Paco Sonia,
Ghezali Gregory,
Ciria Victor,
Pozas Esther,
Ferrer Isidro,
Aguado Fernando
Publication year - 2013
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/j.1750-3639.2012.00644.x
Subject(s) - receptor , neurite , alzheimer's disease , microbiology and biotechnology , biology , carboxypeptidase , neurodegeneration , secretion , amyloid (mycology) , neurotrophic factors , neurotrophin , neuroscience , endocrinology , medicine , biochemistry , disease , botany , in vitro , enzyme
The secretory sorting receptors carboxypeptidase E ( CPE ) and secretogranin III ( SgIII ) critically activate peptidic messengers and targeting them at the regulated secretory pathway. In A lzheimer's disease ( AD ), the wide range of changes includes impaired function of key secretory peptidic cargos such as brain‐derived neurotrophic factor ( BDNF ) and neuropeptides. Here, we analyzed CPE and SgIII in the cerebral cortex of AD patients and transgenic mice. In the normal human cortex, a preferential location in dendrites and perikarya was observed for CPE , whereas SgIII was mainly associated with axons and terminal‐like buttons. Interestingly, SgIII and CPE were consistently detected in astroglial cell bodies and thin processes. In AD cortices, a strong wide accumulation of both sorting receptors was detected in dystrophic neurites surrounding amyloid plaques. Occasionally, increased levels of SgIII were also observed in plaque associate‐reactive astrocytes. Of note, the main alterations detected for CPE and SgIII in AD patients were faithfully recapitulated by APPswe/PS1dE9 mice. These results implicate for the first time the sorting receptors for regulated secretion in amyloid β‐associated neural degeneration. Because CPE and SgIII are essential in the process and targeting of neuropeptides and neurotrophins, their participation in the pathological progression of AD may be suggested.