Abstract
Alzheimer’s disease (AD) has a profound impact on healthy ageing. It is characterized by the accumulation of a small neuro-toxic peptide, amyloid-beta (Aβ) which forms fibrous plaques within the brain. Interestingly N-terminally truncated forms of Ab constitute 20% of plaque load. Surprisingly very little is known about these truncated forms of Ab. The PhD student will use a large tool-kit of biophysical and spectroscopic techniques to probe, the kinetics of fibre formation, fibre structure and lipid membrane interactions. In addition, electro-physiology will be used investigate ion channel formation to investigate the relationship between N-terminally truncated Ab, cellular toxicity and AD pathology.
References
- Naslund, J.; Schierhorn, A.; Hellman, U.; Lannfelt, L.; Roses, A. D.; Tjernberg, L. O.; Silberring, J.; Gandy, S. E.; Winblad, B.; Greengard, P.; Nordstedt, C.; Terenius, L. RELATIVE ABUNDANCE OF ALZHEIMER A-BETA AMYLOID PEPTIDE VARIANTS IN ALZHEIMER-DISEASE. (1994) Proc of the Nat Acad of Sci. 91, 8378-8382
- Matheou CJ; Younan ND; Viles JH Cu2+ accentuates distinct misfolding of Abeta(1-40) and Abeta(1-42) peptides, and potentiates membrane disruption. (2015) Biochem J. 466, 233-242
- Bode DC, Baker MD, Viles JH Ion Channel Formation by Amyloid-β42 Oligomers but not Amyloid-β40 in Cellular Membranes (2017) J of Biol Chem 292, 1404-1413
- Barritt JD., Viles JH Truncated Amyloid-β (11-40/42) from Alzheimer’s Disease Binds Copper2+ with a Femtomolar Affinity and Influences Fibre Assembly. (2015) J of Biol Chem. 290, 27791-27802
- Matheou CJ, Younan ND, Viles JH. The Rapid Exchange of Zinc2+ Enables Trace Levels to Profoundly Influence Amyloid-β Misfolding and Dominates Assembly Outcomes in Cu2+/Zn2+ Mixtures (2016) J Mol Biol 428, 2832-2846