Amyloid Beta Aggregation in the Presence of Temperature-Sensitive Polymers

The formation of amyloid fibrils is considered to be one of the main causes for many neurodegenerative diseases, such as Alzheimer’s, Parkinson’s or Huntington’s disease. Current knowledge suggests that amyloid-aggregation represents a nucleation-dependent aggregation process in vitro, where a sigmo...

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Main Authors: Sebastian Funtan, Zhanna Evgrafova, Juliane Adler, Daniel Huster, Wolfgang H. Binder
Format: Article
Language:English
Published: MDPI AG 2016-05-01
Series:Polymers
Subjects:
Online Access:http://www.mdpi.com/2073-4360/8/5/178
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author Sebastian Funtan
Zhanna Evgrafova
Juliane Adler
Daniel Huster
Wolfgang H. Binder
author_facet Sebastian Funtan
Zhanna Evgrafova
Juliane Adler
Daniel Huster
Wolfgang H. Binder
author_sort Sebastian Funtan
collection DOAJ
description The formation of amyloid fibrils is considered to be one of the main causes for many neurodegenerative diseases, such as Alzheimer’s, Parkinson’s or Huntington’s disease. Current knowledge suggests that amyloid-aggregation represents a nucleation-dependent aggregation process in vitro, where a sigmoidal growth phase follows an induction period. Here, we studied the fibrillation of amyloid β 1-40 (Aβ40) in the presence of thermoresponsive polymers, expected to alter the Aβ40 fibrillation kinetics due to their lower critical solution behavior. To probe the influence of molecular weight and the end groups of the polymer on its lower critical solution temperature (LCST), also considering its concentration dependence in the presence of buffer-salts needed for the aggregation studies of the amyloids, poly(oxazolines) (POx) with LCSTs ranging from 14.2–49.8 °C and poly(methoxy di(ethylene glycol)acrylates) with LCSTs ranging from 34.4–52.7 °C were synthesized. The two different polymers allowed the comparison of the influence of different molecular structures onto the fibrillation process. Mixtures of Aβ40 with these polymers in varying concentrations were studied via time-dependent measurements of the thioflavin T (ThT) fluorescence. The studies revealed that amyloid fibrillation was accelerated in, accompanied by an extension of the lag phase of Aβ40 fibrillation from 18.3 h in the absence to 19.3 h in the presence of the poly(methoxy di(ethylene glycol)acrylate) (3600 g/mol).
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spelling doaj.art-4712538aabd64bf98971a9d50405f88e2022-12-22T03:42:32ZengMDPI AGPolymers2073-43602016-05-018517810.3390/polym8050178polym8050178Amyloid Beta Aggregation in the Presence of Temperature-Sensitive PolymersSebastian Funtan0Zhanna Evgrafova1Juliane Adler2Daniel Huster3Wolfgang H. Binder4Faculty of Natural Science II, Martin-Luther University Halle-Wittenberg, Von-Danckelmann-Platz 4, D-06120 Halle (Saale), GermanyFaculty of Natural Science II, Martin-Luther University Halle-Wittenberg, Von-Danckelmann-Platz 4, D-06120 Halle (Saale), GermanyInstitute for Medical Physics and Biophysics, Leipzig University, Härtelstraße 16-18, D-04107 Leipzig, GermanyInstitute for Medical Physics and Biophysics, Leipzig University, Härtelstraße 16-18, D-04107 Leipzig, GermanyFaculty of Natural Science II, Martin-Luther University Halle-Wittenberg, Von-Danckelmann-Platz 4, D-06120 Halle (Saale), GermanyThe formation of amyloid fibrils is considered to be one of the main causes for many neurodegenerative diseases, such as Alzheimer’s, Parkinson’s or Huntington’s disease. Current knowledge suggests that amyloid-aggregation represents a nucleation-dependent aggregation process in vitro, where a sigmoidal growth phase follows an induction period. Here, we studied the fibrillation of amyloid β 1-40 (Aβ40) in the presence of thermoresponsive polymers, expected to alter the Aβ40 fibrillation kinetics due to their lower critical solution behavior. To probe the influence of molecular weight and the end groups of the polymer on its lower critical solution temperature (LCST), also considering its concentration dependence in the presence of buffer-salts needed for the aggregation studies of the amyloids, poly(oxazolines) (POx) with LCSTs ranging from 14.2–49.8 °C and poly(methoxy di(ethylene glycol)acrylates) with LCSTs ranging from 34.4–52.7 °C were synthesized. The two different polymers allowed the comparison of the influence of different molecular structures onto the fibrillation process. Mixtures of Aβ40 with these polymers in varying concentrations were studied via time-dependent measurements of the thioflavin T (ThT) fluorescence. The studies revealed that amyloid fibrillation was accelerated in, accompanied by an extension of the lag phase of Aβ40 fibrillation from 18.3 h in the absence to 19.3 h in the presence of the poly(methoxy di(ethylene glycol)acrylate) (3600 g/mol).http://www.mdpi.com/2073-4360/8/5/178amyloid βfibrillationlower critical solution temperaturethermoresponsive polymer
spellingShingle Sebastian Funtan
Zhanna Evgrafova
Juliane Adler
Daniel Huster
Wolfgang H. Binder
Amyloid Beta Aggregation in the Presence of Temperature-Sensitive Polymers
Polymers
amyloid β
fibrillation
lower critical solution temperature
thermoresponsive polymer
title Amyloid Beta Aggregation in the Presence of Temperature-Sensitive Polymers
title_full Amyloid Beta Aggregation in the Presence of Temperature-Sensitive Polymers
title_fullStr Amyloid Beta Aggregation in the Presence of Temperature-Sensitive Polymers
title_full_unstemmed Amyloid Beta Aggregation in the Presence of Temperature-Sensitive Polymers
title_short Amyloid Beta Aggregation in the Presence of Temperature-Sensitive Polymers
title_sort amyloid beta aggregation in the presence of temperature sensitive polymers
topic amyloid β
fibrillation
lower critical solution temperature
thermoresponsive polymer
url http://www.mdpi.com/2073-4360/8/5/178
work_keys_str_mv AT sebastianfuntan amyloidbetaaggregationinthepresenceoftemperaturesensitivepolymers
AT zhannaevgrafova amyloidbetaaggregationinthepresenceoftemperaturesensitivepolymers
AT julianeadler amyloidbetaaggregationinthepresenceoftemperaturesensitivepolymers
AT danielhuster amyloidbetaaggregationinthepresenceoftemperaturesensitivepolymers
AT wolfganghbinder amyloidbetaaggregationinthepresenceoftemperaturesensitivepolymers