Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
The APP processing enzyme ADAM10 is up-regulated by retinoic acid in a PI3-kinase-dependent manner
Stockholm University, Faculty of Science, Department of Neurochemistry.
Stockholm University, Faculty of Science, Department of Neurochemistry.
Stockholm University, Faculty of Science, Department of Neurochemistry.
Stockholm University, Faculty of Science, Department of Neurochemistry.ORCID iD: 0000-0002-0308-1964
(English)In: FEBS Letters, ISSN 0014-5793, E-ISSN 1873-3468Article in journal (Refereed) Submitted
National Category
Biochemistry and Molecular Biology
Identifiers
URN: urn:nbn:se:su:diva-24196OAI: oai:DiVA.org:su-24196DiVA: diva2:196996
Available from: 2007-04-19 Created: 2007-04-11 Last updated: 2015-03-09
In thesis
1. Processing of the amyloid precursor protein and its paralogues amyloid precursor-like proteins 1 and 2
Open this publication in new window or tab >>Processing of the amyloid precursor protein and its paralogues amyloid precursor-like proteins 1 and 2
2007 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Alzheimer’s disease (AD) is a neurodegenerative disorder which is histopathologically characterised by amyloid plaques and neurofibrillary tangles. Amyloid plaques consist of the amyloid β-peptide (Aβ) that can form aggregates in the brain. Aβ is generated from the amyloid precursor protein (APP) through proteolytic cleavage. APP belongs to a conserved protein family that also includes the two paralogues, APP-like proteins 1 and 2 (APLP1 and APLP2). Despite the immense amount of research on APP, motivated by its implication in AD, the function of this protein family has not yet been determined. In this thesis, we have studied the expression and proteolytic processing of the APP protein family. Our results are consistent with previous findings that suggest a role for APP during neuronal development. Treatment of cells with retinoic acid (RA) resulted in increased synthesis. In addition, we observed that RA treatment shifted the processing of APP from the amyloidogenic to the non-amyloidogenic pathway. The proteins in the APP family have been hard to distinguish both with respect to function and proteolytic processing. However, for development of new drugs with APP processing enzymes as targets this is of great importance. Our studies suggest similarities, but also differences in the mechanism regulating the processing of the different paralogues. We found that brain-derived neurotrophic factor (BDNF) had different impact on the members of the APP family. Most interestingly, we also found that the mechanism behind the increased processing in response to IGF-1 was not identical between the homologous proteins. In summary, our results indicate that in terms of regulation APLP1 and APLP2 differ more from each other than from APP. Our studies open up the possibility of finding means to selectively block Aβ production without interfering with the processing and function of the paralogous proteins.

Place, publisher, year, edition, pages
Stockholm: Institutionen för neurokemi, 2007. 89 p.
Keyword
APP, APLP1, APLP2, Alzheimer's disease, Amyloid β-peptide, Processing, RA, BDNF, IGF-1, curcumin, PI3-K, MAPK, cdk5
National Category
Neurosciences
Research subject
Neurochemistry and Molecular Neurobiology
Identifiers
urn:nbn:se:su:diva-6763 (URN)978-91-7155-417-8 (ISBN)
Public defence
2007-05-11, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 12 A, Stockholm, 10:00 (English)
Opponent
Supervisors
Available from: 2007-04-19 Created: 2007-04-11 Last updated: 2010-01-12Bibliographically approved

Open Access in DiVA

No full text

Search in DiVA

By author/editor
Iverfeldt, Kerstin
By organisation
Department of Neurochemistry
In the same journal
FEBS Letters
Biochemistry and Molecular Biology

Search outside of DiVA

GoogleGoogle Scholar

urn-nbn

Altmetric score

urn-nbn
Total: 85 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf