Display Settings:

Format

Send to:

Choose Destination
Neurobiol Aging. 2011 Aug;32(8):1435-42. doi: 10.1016/j.neurobiolaging.2009.08.013. Epub 2009 Sep 20.

Cystatin C is released in association with exosomes: a new tool of neuronal communication which is unbalanced in Alzheimer's disease.

Author information

  • 1Proteomics Unit, IRCCS, Centro S.Giovanni di Dio-Fatebenefratelli, Brescia, Italy. rghidoni@fatebenefratelli.it

Abstract

It has recently become clear that proteins associated with neurodegenerative disorders can be selectively incorporated into intraluminal vesicles of multivesicular bodies and subsequently released within exosomes. Multiple lines of research support a neuroprotective role for cystatin C in Alzheimer's disease (AD). Herein we demonstrate that cystatin C, a protein targeted to the classical secretory pathway by its signal peptide sequence, is also secreted by mouse primary neurons in association with exosomes. Immunoproteomic analysis using SELDI-TOF MS revealed the presence in exosomes of at least 9 different cystatin C glycoforms. Moreover, the over-expression of familial AD-associated presenilin 2 mutations (PS2 M239I and PS2 T122R) resulted in reduced levels of all cystatin C forms (native and glycosylated) and of amyloid-β precursor protein (APP) metabolites within exosomes. A better understanding of the mechanisms involved in exosomal processing and release may have important implications for the fight against AD and other neurodegenerative diseases.

Copyright © 2009 Elsevier Inc. All rights reserved.

PMID:
19773092
[PubMed - indexed for MEDLINE]
PMCID:
PMC2891183
Free PMC Article

Images from this publication.See all images (4)Free text

Fig. 1
Fig. 2
Fig. 3
Fig. 4
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk