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Acta Neuropathologica Communications
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Acta Neuropathologica Communications
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Enhanced exosome secretion in Down syndrome brain - a protective mechanism to alleviate neuronal endosomal abnormalities

Authors: Sebastien A. Gauthier; Rocío Pérez-González; Ajay Sharma; Fang-Ke Huang; Melissa J. Alldred; Monika Pawlik; Gurjinder Kaur; +3 Authors

Enhanced exosome secretion in Down syndrome brain - a protective mechanism to alleviate neuronal endosomal abnormalities

Abstract

A dysfunctional endosomal pathway and abnormally enlarged early endosomes in neurons are an early characteristic of Down syndrome (DS) and Alzheimer’s disease (AD). We have hypothesized that endosomal material can be released by endosomal multivesicular bodies (MVBs) into the extracellular space via exosomes to relieve neurons of accumulated endosomal contents when endosomal pathway function is compromised. Supporting this, we found that exosome secretion is enhanced in the brains of DS patients and a mouse model of the disease, and by DS fibroblasts. Furthermore, increased levels of the tetraspanin CD63, a regulator of exosome biogenesis, were observed in DS brains. Importantly, CD63 knockdown diminished exosome release and worsened endosomal pathology in DS fibroblasts. Taken together, these data suggest that increased CD63 expression enhances exosome release as an endogenous mechanism mitigating endosomal abnormalities in DS. Thus, the upregulation of exosome release represents a potential therapeutic goal for neurodegenerative disorders with endosomal pathology. Electronic supplementary material The online version of this article (doi:10.1186/s40478-017-0466-0) contains supplementary material, which is available to authorized users.

Subjects by Vocabulary

Microsoft Academic Graph classification: Endosome Biology Exosome Downregulation and upregulation Tetraspanin Secretion Gene knockdown Extracellular vesicle Microvesicles Cell biology

Library of Congress Subject Headings: lcsh:RC346-429 lcsh:Neurology. Diseases of the nervous system

Keywords

Adult, Male, Down syndrome, Mice, Transgenic, Exosomes, Pathology and Forensic Medicine, Cellular and Molecular Neuroscience, CD63, Animals, Humans, exosome, RNA, Messenger, endosome, Cells, Cultured, Aged, Tetraspanin 30, Research, Brain, Fibroblasts, Middle Aged, Neuroprotection, rab35, Disease Models, Animal, rab GTP-Binding Proteins, Female, extracellular vesicle, Neurology (clinical)

56 references, page 1 of 6

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  • citations
    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    101
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 1%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Top 10%
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 1%
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
101
Top 1%
Top 10%
Top 1%
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NIH| CORE--STATISTICS AND DATA MANAGEMENT
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  • Funder: National Institutes of Health (NIH)
  • Project Code: 1P01AG014449-02
  • Funding stream: NATIONAL INSTITUTE ON AGING
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NIH| Protein Mass Spectrometry Core Facility for Neuroscience
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  • Project Code: 5P30NS050276-02
  • Funding stream: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
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NIH| Cell and molecular pathobiology of Alzheimers Disease
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  • Funder: National Institutes of Health (NIH)
  • Project Code: 3P01AG017617-07S1
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NIH| Cellular and Molecular Medial Temporal Lobe Pathology in Elderly PreMCI subjects
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  • Funder: National Institutes of Health (NIH)
  • Project Code: 7R01AG043375-03
  • Funding stream: NATIONAL INSTITUTE ON AGING
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