Journal
CHEMISTRY & BIOLOGY
Volume 21, Issue 6, Pages 732-742Publisher
CELL PRESS
DOI: 10.1016/j.chembiol.2014.03.014
Keywords
-
Categories
Funding
- Wenner-Gren Foundation
- EPSRC
- Alzheimer Research UK Trust
- Wellcome Trust
- Medical Research Council
- Alzheimers Research UK [ARUK-PG2013-14] Funding Source: researchfish
- Engineering and Physical Sciences Research Council [EP/H018301/1] Funding Source: researchfish
- Medical Research Council [MC_G1000734] Funding Source: researchfish
- EPSRC [EP/H018301/1] Funding Source: UKRI
- MRC [MC_G1000734] Funding Source: UKRI
Ask authors/readers for more resources
Insight into how amyloid beta (A beta) aggregation occurs in vivo is vital for understanding the molecular pathways that underlie Alzheimer's disease and requires new techniques that provide detailed kinetic and mechanistic information. Using noninvasive fluorescence lifetime recordings, we imaged the formation of A beta(1-40) and A beta(1-42) aggregates in live cells. For both peptides, the cellular uptake via endocytosis is rapid and spontaneous. They are then retained in lysosomes, where their accumulation leads to aggregation. The kinetics of A beta(1-42) aggregation are considerably faster than those of A beta(1-40) and, unlike those of the latter peptide, show no detectable lag phase. We used superresolution fluorescence imaging to examine the resulting aggregates and could observe compact amyloid structures, likely because of spatial confinement within cellular compartments. Taken together, these findings provide clues as to how A beta aggregation may occur within neurons.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available