title: 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.
authors.affiliation: Department of Cell Biology, University of Barcelona, Barcelona, Spain.
authors.forename: Virginia
authors.initials: V
authors.lastname: Plá
authors.forename: Sonia
authors.initials: S
authors.lastname: Paco
authors.forename: Gregory
authors.initials: G
authors.lastname: Ghezali
authors.forename: Victor
authors.initials: V
authors.lastname: Ciria
authors.forename: Esther
authors.initials: E
authors.lastname: Pozas
authors.forename: Isidro
authors.initials: I
authors.lastname: Ferrer
authors.forename: Fernando
authors.initials: F
authors.lastname: Aguado
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D015153:Blotting, Western; D043423:Carboxypeptidase H / Q000235:genetics* / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D002864:Chromogranins / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D008875:Middle Aged; D009410:Nerve Degeneration / Q000378:metabolism* / Q000473:pathology*; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology
chemical_list: D016229:Amyloid beta-Peptides; D002864:Chromogranins; D005904:Glial Fibrillary Acidic Protein; C506167:secretogranin III; D043423:Carboxypeptidase H