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Secretory sorting receptors carboxypeptidase E and secretogranin III in amyloid β-associated neural degeneration in Alzheimer's disease.

Abstract
The secretory sorting receptors carboxypeptidase E (CPE) and secretogranin III (SgIII) critically activate peptidic messengers and targeting them at the regulated secretory pathway. In Alzheimer'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.
AuthorsVirginia Plá, Sonia Paco, Gregory Ghezali, Victor Ciria, Esther Pozas, Isidro Ferrer, Fernando Aguado
JournalBrain pathology (Zurich, Switzerland) (Brain Pathol) Vol. 23 Issue 3 Pg. 274-84 (May 2013) ISSN: 1750-3639 [Electronic] Switzerland
PMID22998035 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2012 The Authors; Brain Pathology © 2012 International Society of Neuropathology.
Chemical References
  • Amyloid beta-Peptides
  • Chromogranins
  • Glial Fibrillary Acidic Protein
  • secretogranin III
  • Carboxypeptidase H
Topics
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease (metabolism, pathology)
  • Amyloid beta-Peptides (genetics, metabolism)
  • Animals
  • Astrocytes (metabolism, pathology)
  • Blotting, Western
  • Carboxypeptidase H (genetics, metabolism)
  • Cerebral Cortex (metabolism, pathology)
  • Chromogranins (genetics, metabolism)
  • Female
  • Glial Fibrillary Acidic Protein (metabolism)
  • Humans
  • Immunohistochemistry
  • Male
  • Mice
  • Mice, Transgenic
  • Microscopy, Electron
  • Middle Aged
  • Nerve Degeneration (metabolism, pathology)
  • Plaque, Amyloid (metabolism, pathology)

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