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Differential Stimul...
Differential Stimulation of Pluripotent Stem Cell-Derived Human Microglia Leads to Exosomal Proteomic Changes Affecting Neurons
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Mallach, A. (författare)
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- Gobom, Johan (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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Arber, C. (författare)
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Piers, T. M. (författare)
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Hardy, J. (författare)
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Wray, S. (författare)
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- Zetterberg, Henrik, 1973 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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Pocock, J. (författare)
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(creator_code:org_t)
- 2021-10-24
- 2021
- Engelska.
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Ingår i: Cells. - : MDPI AG. - 2073-4409. ; 10:11
- Relaterad länk:
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https://www.mdpi.com...
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https://gup.ub.gu.se...
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https://doi.org/10.3...
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Abstract
Ämnesord
Stäng
- Microglial exosomes are an emerging communication pathway, implicated in fulfilling homeostatic microglial functions and transmitting neurodegenerative signals. Gene variants of triggering receptor expressed on myeloid cells-2 (TREM2) are associated with an increased risk of developing dementia. We investigated the influence of the TREM2 Alzheimer's disease risk variant, R47H(het), on the microglial exosomal proteome consisting of 3019 proteins secreted from human iPS-derived microglia (iPS-Mg). Exosomal protein content changed according to how the iPS-Mg were stimulated. Thus lipopolysaccharide (LPS) induced microglial exosomes to contain more inflammatory signals, whilst stimulation with the TREM2 ligand phosphatidylserine (PS+) increased metabolic signals within the microglial exosomes. We tested the effect of these exosomes on neurons and found that the exosomal protein changes were functionally relevant and influenced downstream functions in both neurons and microglia. Exosomes from R47H(het) iPS-Mg contained disease-associated microglial (DAM) signature proteins and were less able to promote the outgrowth of neuronal processes and increase mitochondrial metabolism in neurons compared with exosomes from the common TREM2 variant iPS-Mg. Taken together, these data highlight the importance of microglial exosomes in fulfilling microglial functions. Additionally, variations in the exosomal proteome influenced by the R47H(het) TREM2 variant may underlie the increased risk of Alzheimer's disease associated with this variant.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Nyckelord
- dementia
- Alzheimer's disease
- exosomes
- microglia
- proteome
- intercellular signalling
- cutting edge
- amyloid-beta
- trem2
- inhibition
- suggests
- variants
- sh-sy5y
- disease
- binding
- Cell Biology
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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