Amyloid β Oligomeric Species Present in the Lag Phase of Amyloid Formation.
Alzheimer's disease (AD)-associated amyloid β peptide (Aβ) is one of the main actors in AD pathogenesis. Aβ is characterized by its high tendency to self-associate, leading to the generation of oligomers and amyloid fibrils. The elucidation of pathways and intermediates is crucial for the under...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2015-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4449029?pdf=render |
| _version_ | 1818060199765737472 |
|---|---|
| author | Martin Wolff Dmitry Unuchek Bo Zhang Valentin Gordeliy Dieter Willbold Luitgard Nagel-Steger |
| author_facet | Martin Wolff Dmitry Unuchek Bo Zhang Valentin Gordeliy Dieter Willbold Luitgard Nagel-Steger |
| author_sort | Martin Wolff |
| collection | DOAJ |
| description | Alzheimer's disease (AD)-associated amyloid β peptide (Aβ) is one of the main actors in AD pathogenesis. Aβ is characterized by its high tendency to self-associate, leading to the generation of oligomers and amyloid fibrils. The elucidation of pathways and intermediates is crucial for the understanding of protein assembly mechanisms in general and in conjunction with neurodegenerative diseases, e.g., for the identification of new therapeutic targets. Our study focused on Aβ42 and its oligomeric assemblies in the lag phase of amyloid formation, as studied by sedimentation velocity (SV) centrifugation. The assembly state of Aβ during the lag phase, the time required by an Aβ solution to reach the exponential growth phase of aggregation, was characterized by a dominant monomer fraction below 1 S and a population of oligomeric species between 4 and 16 S. From the oligomer population, two major species close to a 12-mer and an 18-mer with a globular shape were identified. The recurrence of these two species at different initial concentrations and experimental conditions as the smallest assemblies present in solution supports the existence of distinct, energetically favored assemblies in solution. The sizes of the two species suggest an Aβ42 aggregation pathway that is based on a basic hexameric building block. The study demonstrates the potential of SV analysis for the evaluation of protein aggregation pathways. |
| first_indexed | 2024-12-10T13:28:38Z |
| format | Article |
| id | doaj.art-9f7b66f6a4044bce92c49479c8452f75 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T13:28:38Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-9f7b66f6a4044bce92c49479c8452f752022-12-22T01:47:05ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01105e012786510.1371/journal.pone.0127865Amyloid β Oligomeric Species Present in the Lag Phase of Amyloid Formation.Martin WolffDmitry UnuchekBo ZhangValentin GordeliyDieter WillboldLuitgard Nagel-StegerAlzheimer's disease (AD)-associated amyloid β peptide (Aβ) is one of the main actors in AD pathogenesis. Aβ is characterized by its high tendency to self-associate, leading to the generation of oligomers and amyloid fibrils. The elucidation of pathways and intermediates is crucial for the understanding of protein assembly mechanisms in general and in conjunction with neurodegenerative diseases, e.g., for the identification of new therapeutic targets. Our study focused on Aβ42 and its oligomeric assemblies in the lag phase of amyloid formation, as studied by sedimentation velocity (SV) centrifugation. The assembly state of Aβ during the lag phase, the time required by an Aβ solution to reach the exponential growth phase of aggregation, was characterized by a dominant monomer fraction below 1 S and a population of oligomeric species between 4 and 16 S. From the oligomer population, two major species close to a 12-mer and an 18-mer with a globular shape were identified. The recurrence of these two species at different initial concentrations and experimental conditions as the smallest assemblies present in solution supports the existence of distinct, energetically favored assemblies in solution. The sizes of the two species suggest an Aβ42 aggregation pathway that is based on a basic hexameric building block. The study demonstrates the potential of SV analysis for the evaluation of protein aggregation pathways.http://europepmc.org/articles/PMC4449029?pdf=render |
| spellingShingle | Martin Wolff Dmitry Unuchek Bo Zhang Valentin Gordeliy Dieter Willbold Luitgard Nagel-Steger Amyloid β Oligomeric Species Present in the Lag Phase of Amyloid Formation. PLoS ONE |
| title | Amyloid β Oligomeric Species Present in the Lag Phase of Amyloid Formation. |
| title_full | Amyloid β Oligomeric Species Present in the Lag Phase of Amyloid Formation. |
| title_fullStr | Amyloid β Oligomeric Species Present in the Lag Phase of Amyloid Formation. |
| title_full_unstemmed | Amyloid β Oligomeric Species Present in the Lag Phase of Amyloid Formation. |
| title_short | Amyloid β Oligomeric Species Present in the Lag Phase of Amyloid Formation. |
| title_sort | amyloid β oligomeric species present in the lag phase of amyloid formation |
| url | http://europepmc.org/articles/PMC4449029?pdf=render |
| work_keys_str_mv | AT martinwolff amyloidboligomericspeciespresentinthelagphaseofamyloidformation AT dmitryunuchek amyloidboligomericspeciespresentinthelagphaseofamyloidformation AT bozhang amyloidboligomericspeciespresentinthelagphaseofamyloidformation AT valentingordeliy amyloidboligomericspeciespresentinthelagphaseofamyloidformation AT dieterwillbold amyloidboligomericspeciespresentinthelagphaseofamyloidformation AT luitgardnagelsteger amyloidboligomericspeciespresentinthelagphaseofamyloidformation |