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Direct Observations of Amyloid beta Self-Assembly in Live Cells Provide Insights into Differences in the Kinetics of A beta(1-40) and A beta(1-42) Aggregation

Elin Esbjörner (Institutionen för kemi- och bioteknik, Fysikalisk kemi) ; F. Chan ; E. Rees ; M. Erdelyi ; L. M. Luheshi ; C. W. Bertoncini ; C. F. Kaminski ; C. M. Dobson ; G. S. K. Schierle
Chemistry & Biology (1074-5521). Vol. 21 (2014), 6, p. 732-742.
[Artikel, refereegranskad vetenskaplig]

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.

Nyckelord: ALZHEIMERS-DISEASE, INTRINSIC FLUORESCENCE, ALPHA-SYNUCLEIN, HUMAN, BRAIN, PROTEIN, FIBRILS, PEPTIDE, OLIGOMERS, GROWTH, ACCUMULATION, Biochemistry & Molecular Biology



Denna post skapades 2014-07-24. Senast ändrad 2014-11-03.
CPL Pubid: 200692

 

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Institutioner (Chalmers)

Institutionen för kemi- och bioteknik, Fysikalisk kemi (2005-2014)

Ämnesområden

Organisk kemi
Medicinsk bioteknologi (med inriktning mot cellbiologi)

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