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Amyloid-β deposits ...
Amyloid-β deposits in human astrocytes contain truncated and highly resistant proteoforms
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- Beretta, Chiara (författare)
- Uppsala universitet,Molekylär geriatrik
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- Svensson, Elina (författare)
- Uppsala universitet,Molekylär geriatrik,Department of Neuroinflammation, UCL Queen Square Institute of Neurology, 1 Wakefield Street, WC1N 1PJ London, United Kingdom of Great Britain and Northern Ireland
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- Dakhel, Abdulkhalek (författare)
- Uppsala universitet,Molekylär geriatrik
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- Zyśk, Marlena (författare)
- Uppsala universitet,Molekylär geriatrik
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- Hanrieder, Jörg, 1980 (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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- Sehlin, Dag, 1976- (författare)
- Uppsala universitet,Molekylär geriatrik
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- Michno, Wojciech (författare)
- Uppsala universitet,Molekylär geriatrik,Science for Life Laboratory, SciLifeLab
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- Erlandsson, Anna (författare)
- Uppsala universitet,Molekylär geriatrik
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(creator_code:org_t)
- Elsevier, 2024
- 2024
- Engelska.
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Ingår i: Molecular and Cellular Neuroscience. - : Elsevier. - 1044-7431 .- 1095-9327. ; 128
- Relaterad länk:
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://gup.ub.gu.se...
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Abstract
Ämnesord
Stäng
- Alzheimer's disease (AD) is a neurodegenerative disorder that develops over decades. Glial cells, including astrocytes are tightly connected to the AD pathogenesis, but their impact on disease progression is still unclear. Our previous data show that astrocytes take up large amounts of aggregated amyloid-beta (Aβ) but are unable to successfully degrade the material, which is instead stored intracellularly. The aim of the present study was to analyze the astrocytic Aβ deposits composition in detail in order to understand their role in AD propagation. For this purpose, human induced pluripotent cell (hiPSC)-derived astrocytes were exposed to sonicated Aβ42 fibrils and magnetic beads. Live cell imaging and immunocytochemistry confirmed that the ingested Aβ aggregates and beads were transported to the same lysosomal compartments in the perinuclear region, which allowed us to successfully isolate the Aβ deposits from the astrocytes. Using a battery of experimental techniques, including mass spectrometry, western blot, ELISA and electron microscopy we demonstrate that human astrocytes truncate and pack the Aβ aggregates in a way that makes them highly resistant. Moreover, the astrocytes release specifically truncated forms of Aβ via different routes and thereby expose neighboring cells to pathogenic proteins. Taken together, our study establishes a role for astrocytes in mediating Aβ pathology, which could be of relevance for identifying novel treatment targets for AD.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Annan medicin och hälsovetenskap -- Övrig annan medicin och hälsovetenskap (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Other Medical and Health Sciences -- Other Medical and Health Sciences not elsewhere specified (hsv//eng)
- NATURVETENSKAP -- Biologi -- Annan biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Other Biological Topics (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Nyckelord
- Alzheimer's disease
- Amyloid β
- Astrocytes
- Aggregate
- Amyloid beta
- Astrocytes
- Aggregate
- Alzheimer's disease
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Beretta, Chiara
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Svensson, Elina
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Dakhel, Abdulkha ...
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Zyśk, Marlena
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Hanrieder, Jörg, ...
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Sehlin, Dag, 197 ...
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visa fler...
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Michno, Wojciech
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Erlandsson, Anna
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visa färre...
- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Annan medicin oc ...
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och Övrig annan medi ...
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- NATURVETENSKAP
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NATURVETENSKAP
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och Biologi
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och Annan biologi
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinska och f ...
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och Neurovetenskaper
- Artiklar i publikationen
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Molecular and Ce ...
- Av lärosätet
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Uppsala universitet
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Göteborgs universitet