Cystatin C is released in association with exosomes

A new tool of neuronal communication which is unbalanced in Alzheimer's disease

Roberta Ghidoni, Anna Paterlini, Valentina Albertini, Michela Glionna, Eugenio Monti, Luisa Schiaffonati, Luisa Benussi, Efrat Levy, Giuliano Binetti

Research output: Contribution to journalArticle

54 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1435-1442
Number of pages8
JournalNeurobiology of Aging
Volume32
Issue number8
DOIs
Publication statusPublished - Aug 2011

Fingerprint

Exosomes
Cystatin C
Alzheimer Disease
Communication
Neurodegenerative Diseases
Presenilin-2
Multivesicular Bodies
Amyloid beta-Protein Precursor
Secretory Pathway
Matrix-Assisted Laser Desorption-Ionization Mass Spectrometry
Protein Sorting Signals
Proteins
Neurons
Mutation

Keywords

  • APP
  • Cystatin C
  • Electron microscopy
  • Exosomes
  • Glycosylation
  • Presenilin 2 mutations
  • SELDI-TOF MS

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Ageing
  • Developmental Biology
  • Geriatrics and Gerontology

Cite this

Cystatin C is released in association with exosomes : A new tool of neuronal communication which is unbalanced in Alzheimer's disease. / Ghidoni, Roberta; Paterlini, Anna; Albertini, Valentina; Glionna, Michela; Monti, Eugenio; Schiaffonati, Luisa; Benussi, Luisa; Levy, Efrat; Binetti, Giuliano.

In: Neurobiology of Aging, Vol. 32, No. 8, 08.2011, p. 1435-1442.

Research output: Contribution to journalArticle

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