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Social and Behavioral Sciences Commons™
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Full-Text Articles in Social and Behavioral Sciences
Macroglobulin And Haptoglobin Suppress Amyloid Formation By Interacting With Prefibrillar Protein Species, Justin J. Yerbury, Janet R. Kumita, Sarah Meehan, Christopher M. Dobson, Mark R. Wilson
Macroglobulin And Haptoglobin Suppress Amyloid Formation By Interacting With Prefibrillar Protein Species, Justin J. Yerbury, Janet R. Kumita, Sarah Meehan, Christopher M. Dobson, Mark R. Wilson
Mark R Wilson
α2-Macroglobulin (α2M) and haptoglobin (Hp) are both abundant secreted glycoproteins that are best known for their protease trapping and hemoglobin binding activities, respectively. Like the small heat shock proteins, both these glycoproteins have in common the ability to protect a range of proteins from stress-induced amorphous aggregation and have been described as extracellular chaperones. Using an array of biophysical techniques, this study establishes that in vitro at substoichiometric levels and under physiological conditions α2M and Hp both inhibit the formation of amyloid fibrils from a range of proteins. We also provide evidence that both α2M and Hp interact with prefibrillar …
Potential Roles Of Abundant Extracellular Chaperones In The Control Of Amyloid Formation And Toxicity, Mark R. Wilson, Justin J. Yerbury, Stephen Poon
Potential Roles Of Abundant Extracellular Chaperones In The Control Of Amyloid Formation And Toxicity, Mark R. Wilson, Justin J. Yerbury, Stephen Poon
Mark R Wilson
The in vivo formation of fibrillar proteinaceous deposits called amyloid is associated with more than 40 serious human diseases, collectively referred to as protein deposition diseases. In many cases the amyloid deposits are extracellular and are found associated with newly identified abundant extracellular chaperones (ECs). Evidence is presented suggesting an important regulatory role for ECs in amyloid formation and disposal in the body. A model is presented which proposes that, under normal conditions, ECs stabilize extracellular misfolded proteins by binding to them, and then guide them to specific cell receptors for uptake and subsequent degradation. Thus ECs and their receptors …
Single Molecule Characterization Of The Interactions Between Amyloid-Β Peptides And The Membranes Of Hippocampal Cells, Priyanka Narayan, Kristina A. Ganzinger, James Mccoll, Laura Weimann, Sarah Meehan, Seema Qamar, John A. Carver, Mark R. Wilson, Peter St George-Hyslop, Christopher M. Dobson, David Klenerman
Single Molecule Characterization Of The Interactions Between Amyloid-Β Peptides And The Membranes Of Hippocampal Cells, Priyanka Narayan, Kristina A. Ganzinger, James Mccoll, Laura Weimann, Sarah Meehan, Seema Qamar, John A. Carver, Mark R. Wilson, Peter St George-Hyslop, Christopher M. Dobson, David Klenerman
Mark R Wilson
Oligomers of the 40 and 42 residue amyloid-β peptides (Aβ40 and Aβ42) have been implicated in the neuronal damage and impaired cognitive function associated with Alzheimer’s disease. However, little is known about the specific mechanisms by which these misfolded species induce such detrimental effects on cells. In this work, we use single-molecule imaging techniques to examine the initial interactions between Aβ monomers and oligomers and the membranes of live cells. This highly sensitive method enables the visualization of individual Aβ species on the cell surface and characterization of their oligomerization state, all at biologically relevant, nanomolar concentrations. The results indicate …