Year: 2018
Type: dissertation
Abstract: The amyloid-β (Aβ) peptide is understood to be a critical factor in the pathogenesis of Alzheimer’s disease (AD), with soluble Aβ oligomers (oAβ) observed to be particularly toxic to neurons. For this reason, we undertook an in-depth search for oAβ binders in human brain, taking advantage of advanced mass spectrometry workflows. This analysis revealed the peptide somatostatin (SST) to be the most selective binder to oAβ in affinity capture experiments. Furthermore, SST was observed to interfere with Aβ aggregation kinetics and promote the formation of distinct 50-60 kDa Aβ assemblies. In a follow-up investigation of the SST interactome, it was revealed that SST predominantly binds to several members of the family of P-type ATPases, particularly the Na+/K+-ATPase. Subsequent validation experiments confirmed this interaction and identified a tryptophan residue within SST as critical for binding. These findings bring to light potentially new mechanisms for SST action in normal physiology and AD.
Source: TSpace (University of Toronto)
Author: Michael Solarski
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2923737020