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Exosomes: vehicles for the transfer of toxic proteins associated with neurodegenerative diseases?

作者信息

Bellingham Shayne A, Guo Belinda B, Coleman Bradley M, Hill Andrew F

机构信息

Department of Biochemistry and Molecular Biology, The University of Melbourne Melbourne, VIC 3010, Australia.

出版信息

Front Physiol. 2012 May 3;3:124. doi: 10.3389/fphys.2012.00124. eCollection 2012.


DOI:10.3389/fphys.2012.00124
PMID:22563321
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3342525/
Abstract

Exosomes are small membranous vesicles secreted by a number of cell types including neurons and can be isolated from conditioned cell media or bodily fluids such as urine and plasma. Exosome biogenesis involves the inward budding of endosomes to form multivesicular bodies (MVB). When fused with the plasma membrane, the MVB releases the vesicles into the extracellular environment as exosomes. Proposed functions of these vesicles include roles in cell-cell signaling, removal of unwanted proteins, and the transfer of pathogens between cells. One such pathogen which exploits this pathway is the prion, the infectious particle responsible for the transmissible neurodegenerative diseases such as Creutzfeldt-Jakob disease (CJD) of humans or bovine spongiform encephalopathy (BSE) of cattle. Similarly, exosomes are also involved in the processing of the amyloid precursor protein (APP) which is associated with Alzheimer's disease. Exosomes have been shown to contain full-length APP and several distinct proteolytically cleaved products of APP, including Aβ. In addition, these fragments can be modulated using inhibitors of the proteases involved in APP cleavage. These observations provide further evidence for a novel pathway in which PrP and APP fragments are released from cells. Other proteins such as superoxide dismutase I and alpha-synuclein (involved in amyotrophic lateral sclerosis and Parkinson's disease, respectively) are also found associated with exosomes. This review will focus on the role of exosomes in neurodegenerative disorders and discuss the potential of these vesicles for the spread of neurotoxicity, therapeutics, and diagnostics for these diseases.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee37/3342525/8709753b31bd/fphys-03-00124-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee37/3342525/51c67a66bf55/fphys-03-00124-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee37/3342525/8709753b31bd/fphys-03-00124-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee37/3342525/51c67a66bf55/fphys-03-00124-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee37/3342525/8709753b31bd/fphys-03-00124-g002.jpg

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本文引用的文献

[1]
MicroRNA 146a (miR-146a) is over-expressed during prion disease and modulates the innate immune response and the microglial activation state.

PLoS One. 2012-2-17

[2]
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Nucleic Acids Res. 2012-2-22

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Mol Neurobiol. 2012-8

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J Biol Chem. 2011-11-4

[8]
Upregulation of micro RNA-146a (miRNA-146a), a marker for inflammatory neurodegeneration, in sporadic Creutzfeldt-Jakob disease (sCJD) and Gerstmann-Straussler-Scheinker (GSS) syndrome.

J Toxicol Environ Health A. 2011

[9]
Mechanism of transfer of functional microRNAs between mouse dendritic cells via exosomes.

Blood. 2011-10-26

[10]
Exogenous α-synuclein fibrils induce Lewy body pathology leading to synaptic dysfunction and neuron death.

Neuron. 2011-10-6

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