Sökning: onr:"swepub:oai:DiVA.org:uu-354346" >
The A beta protofib...
The A beta protofibril selective antibody mAb158 prevents accumulation of A beta in astrocytes and rescues neurons from A beta-induced cell death
-
- Söllvander, Sofia, 1983- (författare)
- Uppsala universitet,Geriatrik
-
- Nikitidou, Elisabeth (författare)
- Uppsala universitet,Geriatrik
-
- Gallasch, Linn (författare)
- Uppsala universitet,Geriatrik
-
visa fler...
-
- Zysk, Marlena (författare)
- Uppsala universitet,Geriatrik
-
- Söderberg, Linda (författare)
- BioArctic AB, Warfvinges Vag 35, SE-11251 Stockholm, Sweden
-
- Sehlin, Dag, 1976- (författare)
- Uppsala universitet,Geriatrik
-
- Lannfelt, Lars (författare)
- Uppsala universitet,Geriatrik
-
- Erlandsson, Anna (författare)
- Uppsala universitet,Geriatrik
-
visa färre...
-
(creator_code:org_t)
- 2018-03-28
- 2018
- Engelska.
-
Ingår i: Journal of Neuroinflammation. - : BioMed Central. - 1742-2094. ; 15
- Relaterad länk:
-
https://uu.diva-port... (primary) (Raw object)
-
visa fler...
-
https://jneuroinflam...
-
https://urn.kb.se/re...
-
https://doi.org/10.1...
-
visa färre...
Abstract
Ämnesord
Stäng
- Background: Currently, several amyloid beta (A beta) antibodies, including the protofibril selective antibody BAN2401, are in clinical trials. The murine version of BAN2401, mAb158, has previously been shown to lower the levels of pathogenic A beta and prevent A beta deposition in animal models of Alzheimer's disease (AD). However, the cellular mechanisms of the antibody's action remain unknown. We have recently shown that astrocytes effectively engulf A beta(42) protofibrils, but store rather than degrade the ingested A beta aggregates. In a co-culture set-up, the incomplete degradation of A beta(42) protofibrils by astrocytes results in increased neuronal cell death, due to the release of extracellular vesicles, containing N-truncated, neurotoxic A beta. Methods: The aim of the present study was to investigate if the accumulation of A beta in astrocytes can be affected by the A beta protofibril selective antibody mAb158. Co-cultures of astrocytes, neurons, and oligodendrocytes, derived from embryonic mouse cortex, were exposed to A beta(42) protofibrils in the presence or absence of mAb158. Results: Our results demonstrate that the presence of mAb158 almost abolished A beta accumulation in astrocytes. Consequently, mAb158 treatment rescued neurons from A beta-induced cell death. Conclusion: Based on these findings, we conclude that astrocytes may play a central mechanistic role in anti-A beta immunotherapy.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Nyckelord
- Alzheimer's disease
- Amyloid-beta
- Antibody
- Clearance
- Astrocyte
- Neuron
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas