Sökning: onr:"swepub:oai:gup.ub.gu.se/297568" >
Amyloid precursor p...
Amyloid precursor protein processing in human neurons with an allelic series of the PSEN1 intron 4 deletion mutation and total presenilin-1 knockout
-
Arber, C. (författare)
-
Villegas-Llerena, C. (författare)
-
Toombs, J. (författare)
-
visa fler...
-
Pocock, J. M. (författare)
-
Ryan, N. S. (författare)
-
Fox, N. C. (författare)
-
- 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
-
Hardy, J. (författare)
-
Wray, S. (författare)
-
visa färre...
-
(creator_code:org_t)
- 2019-10-14
- 2019
- Engelska.
-
Ingår i: Brain Communications. - : Oxford University Press (OUP). - 2632-1297. ; 1:1
- Relaterad länk:
-
https://academic.oup...
-
visa fler...
-
https://gup.ub.gu.se...
-
https://doi.org/10.1...
-
visa färre...
Abstract
Ämnesord
Stäng
- Mutations in presenilin-1 (PSEN1), encoding the catalytic subunit of the amyloid precursor protein-processing enzyme gamma-secretase, cause familial Alzheimer's disease. However, the mechanism of disease is yet to be fully understood and it remains contentious whether mutations exert their effects predominantly through gain or loss of function. To address this question, we generated an isogenic allelic series for the PSEN1 mutation intron 4 deletion; represented by control, heterozygous and homozygous mutant induced pluripotent stem cells in addition to a presenilin-1 knockout line. Induced pluripotent stem cell-derived cortical neurons reveal reduced, yet detectable amyloid-beta levels in the presenilin-1 knockout line, and a mutant gene dosage-dependent defect in amyloid precursor protein processing in PSEN1 intron 4 deletion lines, consistent with reduced processivity of gamma-secretase. The different effects of presenilin-1 knockout and the PSEN1 intron 4 deletion mutation on amyloid precursor protein-C99 fragment accumulation, nicastrin maturation and amyloid-beta peptide generation support distinct consequences of familial Alzheimer's disease-associated mutations and knockout of presenilin-1 on the function of gamma-secretase.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Nyckelord
- Alzheimer's disease
- iPSCs
- CRISPR/Cas9
- amyloid beta
- familial alzheimers-disease
- secretase
- generate
- Neurosciences & Neurology
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas