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Engineering Amyloid Polypeptide Interactions Relating to Neurodegenerative Disease and Bio Materials
Başlık:
Engineering Amyloid Polypeptide Interactions Relating to Neurodegenerative Disease and Bio Materials
Yazar:
Candreva, Jason T., author.
ISBN:
9780355992540
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (165 pages)
Genel Not:
Source: Dissertation Abstracts International, Volume: 79-10(E), Section: B.
Advisors: Jin R. Kim Committee members: Mary K. Cowman; Rastislav Levicky; Kalle Levon.
Özet:
The objective of this work was to engineer beta-amyloid (Abeta) peptides implicated in Alzheimer's disease (AD) to uncover mechanisms in neurodegenerative disease pathology and develop novel tools for controlled self-assembly of amyloid fibrils. In the first project, I studied Abeta interactions with another amyloid protein, alpha-synuclein (alphaS), which is implicated in Parkinson's disease (PD). Uncovering protein interactions between Abeta and alphaS is important due to the overlap of symptoms seen in AD and PD patients, as well as evidence linking the two pathologies. To achieve this, monomers, oligomers, and fibrils of both Abeta and alphaS were prepared and co-incubated to study their interactions. Abeta and alphaS were conjugated with fluorophores to track their locations within resulting co-assemblies more closely, along with other characterization techniques. This study revealed that alphaS inhibits Abeta fibrillization and stabilizes oligomerization through the Abeta C-terminus. In a second project, I engineered a dual Abeta-variant self-assembly peptide system for the precise control of amyloid assembly, for potential use in the study of size-dependent neurotoxicity and precise fabrication of amyloid biomaterials. The peptides are derived from the hydrophobic central domain of the Abeta peptide, and they are unique in that alone they do not self-assemble but hetero-assemble in the presence of their assembly partner to form amyloid fibrils similar to those formed by Abeta itself. By engineering the peptide termini and optimizing buffer conditions, the assemblies can also be modulated by balancing electrostatic and hydrophobic interactions. Overall, my PhD study reveals that interactions between different species of amyloid peptides can alter aggregation pathways and structures, also paving the way for many novel research applications.
Notlar:
School code: 1988
Tüzel Kişi Ek Girişi:
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Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(681675.1) | 681675-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
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