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Direct Observations...
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
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- Esbjörner Winters, Elin, 1978 (författare)
- Chalmers tekniska högskola,Chalmers University of Technology
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- Chan, F. (författare)
- University Of Cambridge
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- Rees, E. (författare)
- University Of Cambridge
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- Erdelyi, M. (författare)
- University Of Cambridge
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- Luheshi, L. M. (författare)
- University Of Cambridge
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Bertoncini, C. W. (författare)
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- Kaminski, C. F. (författare)
- University Of Cambridge
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- Dobson, C. M. (författare)
- University Of Cambridge
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- Schierle, G. S. K. (författare)
- University Of Cambridge
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(creator_code:org_t)
- Elsevier BV, 2014
- 2014
- Engelska.
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Ingår i: Chemistry and Biology. - : Elsevier BV. - 1074-5521. ; 21:6, s. 732-742
- Relaterad länk:
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http://publications.... (primary) (free)
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https://doi.org/10.1...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
- NATURVETENSKAP -- Kemi -- Organisk kemi (hsv//swe)
- NATURAL SCIENCES -- Chemical Sciences -- Organic Chemistry (hsv//eng)
Nyckelord
- FIBRILS
- BRAIN
- ACCUMULATION
- OLIGOMERS
- ALPHA-SYNUCLEIN
- ALZHEIMERS-DISEASE
- HUMAN
- GROWTH
- PROTEIN
- INTRINSIC FLUORESCENCE
- Biochemistry & Molecular Biology
- PEPTIDE
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- ref (ämneskategori)
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