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Sökning: onr:20859116 > Investigating Amylo...

Investigating Amyloid β toxicity in Drosophila melanogaster [Elektronisk resurs] / Maria Jonson

Jonson, Maria 1981- (författare)
Hammarström, Per 1972- (preses)
Thor, Stefan 1964- (preses)
Dobson, Christopher M (opponent)
Linköpings universitet Institutionen för fysik, kemi och biologi (utgivare)
Alternativt namn: Linköpings universitet. Institutionen för fysik och mätteknik (tidigare namn)
Alternativt namn: Linköpings universitet. Institutionen för fysik och mätteknik, biologi och kemi (tidigare namn)
Alternativt namn: IFM
Alternativt namn: Engelska : Department of Physics and Measurement Technology, Biology and Chemistry
Alternativt namn: Engelska : Department of Physics, Chemistry and Biology
Linköpings universitet Tekniska fakulteten (utgivare)
Linköping Department of Physics, Chemistry and Biology, Linköping University, 2017
Engelska x, 88 s. (PDF)
Serie: Linköping Studies in Science and Technology. Dissertations, 0345-7524 ; 1859
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  • E-bokAvhandling(Diss. (sammanfattning) Linköping : Linköpings universitet, 2017)
Sammanfattning Ämnesord
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  • In this thesis Drosophila melanogaster (the fruit fly) has been used as a model organism to study the aggregation and toxic properties of the human amyloid β (Aβ) peptide involved in the onset of Alzheimer's disease (AD). AD is one of many misfolding diseases where the important event of a protein to adopt its’ specific three-dimensional structure has failed, leading to aggregation and formation of characteristic amyloid fibrils. AD has a complex pathology and probably reflects a variety of related molecular and cellular abnormalities, however, the most apparent common denominator so far is abnormal Amyloid-β precursor protein (APP) processing, resulting in a pool of various Aβ-peptides. In AD, the Aβ peptide misfolds, aggregates and forms amyloid plaques in the brain of patients, resulting in progressive neurodegeneration that eventually leads to death. By expressing the human Aβ protein in the fly, we have studied the mechanisms and toxicity of the aggregation in detail and how different cell types in the fly are affected. We have also used this model to investigate the effect of potential drugs that can have a positive impact on disease progression. In the first and second work in this thesis, we have, in a systematic way, proved that the length of the Aβ-peptide is essential for its toxicity and propensity to aggregate. If the peptide expressed ends at amino acid 42 it is extremely toxic to the fly nervous system. However, this toxicity can be completely abolished by expressing a variant that is shorter than 42 amino acids (1-37 to 1-41 aa), or be significantly reduced by expressing a longer variant (1-43 aa). Toxicity can be partly mitigated in trans by co-expressing the 1-42 variant with a 1-38 variant. This supports the theory that the disease progression could be inhibited if the formation of Aβ 1-42 is decreased. In the third work we demonstrate that amyloid aggregates can be found in various cell types of Drosophila, however, the toxicity seem to be selective to neurons. Our results indicate that the aggregates of glial expressing flies have a more mature structure, which appear to be less toxic. This also suggests that glial cells might spread Aβ aggregates without being harmed. The last work in this thesis investigates how curcumin (turmeric) can affect Aβ aggregation and toxicity. Curcumin appears to shift the equilibrium between the less stable aggregates and mature fibers toward the final stage resulting in an improved lifespan for treated flies. In summary, this thesis demonstrates that the toxicity of Aβ in Drosophila is highly dependent on the Aβ variant expressed, the structure of the protein aggregates and which cell type that expresses the protein. We have also shed light on the potential of using Drosophila when it comes to examining possible therapeutic substances as a tool for drug discovery. 

Ämnesord

Alzheimers sjukdom  (sao)
Proteiner  (sao)
Natural Sciences  (hsv)
Chemical Sciences  (hsv)
Naturvetenskap  (hsv)
Kemi  (hsv)
Medical and Health Sciences  (hsv)
Medical Biotechnology  (hsv)
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)  (hsv)
Medicin och hälsovetenskap  (hsv)
Medicinsk bioteknologi  (hsv)
Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)  (hsv)
Medical and Health Sciences  (hsv)
Basic Medicine  (hsv)
Cell and Molecular Biology  (hsv)
Medicin och hälsovetenskap  (hsv)
Medicinska grundvetenskaper  (hsv)
Cell- och molekylärbiologi  (hsv)
Medical and Health Sciences  (hsv)
Basic Medicine  (hsv)
Pharmacology and Toxicology  (hsv)
Medicin och hälsovetenskap  (hsv)
Medicinska grundvetenskaper  (hsv)
Farmakologi och toxikologi  (hsv)
Alzheimer's disease  (LCSH)
Proteins  (LCSH)

Klassifikation

572.633 (DDC)
Ue.04823 (kssb/8 (machine generated))
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