Structural studies of amyloid-β peptides: Unlocking the mechanism of aggregation and the associated toxicity

Rihards Aleksis; Filips Oleskovs; Kristaps Jaudzems; Jens Pahnke; Henrik Biverstål

doi:10.1016/j.biochi.2017.07.011

Structural studies of amyloid-β peptides: Unlocking the mechanism of aggregation and the associated toxicity

Rihards Aleksis^*, Filips Oleskovs, Kristaps Jaudzems, Jens Pahnke, Henrik Biverstål

^*Corresponding author for this work

Institute of Experimental Dermatology

72 Citations (Scopus)

Abstract

Alzheimer's disease (AD) is one of the most prevalent neurodegenerative diseases worldwide. Formation of amyloid plaques consisting of amyloid-β peptides (Aβ) is one of the hallmarks of AD. Several lines of evidence have shown a correlation between the Aβ aggregation and the disease development. Extensive research has been conducted with the aim to reveal the structures of the neurotoxic Aβ aggregates. However, the exact structure of pathological aggregates and mechanism of the disease still remains elusive due to complexity of the occurring processes and instability of various disease-relevant Aβ species. In this article we review up-to-date structural knowledge about amyloid-β peptides, focusing on data acquired using solution and solid state NMR techniques. Furthermore, we discuss implications from these structural studies on the mechanisms of aggregation and neurotoxicity.

Original language	English
Journal	Biochimie
Volume	140
Pages (from-to)	176-192
Number of pages	17
ISSN	0300-9084
DOIs	https://doi.org/10.1016/j.biochi.2017.07.011
Publication status	Published - 09.2017

Funding

The work of J.P is also funded by Deutsche Forschungsgemeinschaft/Germany (DFG PA930/9, DFG PA930/12); Leibniz Society/Germany (SAW-2015-IPB-2); HelseS?/Norway (2016062); Norsk forskningsr?det/Norway (246392, 247179 (NeuroGeM), 248772, 251290); Horizon 2020/European Union (609020 (Scientia Fellows), 643417 (PROP-AD)). NeuroGeM is an EU Joint Programme - Neurodegenerative Disease Research (JPND) project. The project is supported through the following funding organizations under the aegis of JPND - www.jpnd.eu (CIHR ? Canada, BMBF ? Germany, NRF #247179 ? Norway, ZonMW ? The Netherlands). Scientia Fellows: The research has also received funding from the European Union Seventh Framework Programme (FP7-PEOPLE-2013-COFUND) under grant agreement No 609020.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Research Areas and Centers

Academic Focus: Center for Infection and Inflammation Research (ZIEL)

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Cite this

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title = "Structural studies of amyloid-β peptides: Unlocking the mechanism of aggregation and the associated toxicity",

abstract = "Alzheimer's disease (AD) is one of the most prevalent neurodegenerative diseases worldwide. Formation of amyloid plaques consisting of amyloid-β peptides (Aβ) is one of the hallmarks of AD. Several lines of evidence have shown a correlation between the Aβ aggregation and the disease development. Extensive research has been conducted with the aim to reveal the structures of the neurotoxic Aβ aggregates. However, the exact structure of pathological aggregates and mechanism of the disease still remains elusive due to complexity of the occurring processes and instability of various disease-relevant Aβ species. In this article we review up-to-date structural knowledge about amyloid-β peptides, focusing on data acquired using solution and solid state NMR techniques. Furthermore, we discuss implications from these structural studies on the mechanisms of aggregation and neurotoxicity.",

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AU - Aleksis, Rihards

AU - Oleskovs, Filips

AU - Jaudzems, Kristaps

AU - Pahnke, Jens

AU - Biverstål, Henrik

PY - 2017/9

Y1 - 2017/9

N2 - Alzheimer's disease (AD) is one of the most prevalent neurodegenerative diseases worldwide. Formation of amyloid plaques consisting of amyloid-β peptides (Aβ) is one of the hallmarks of AD. Several lines of evidence have shown a correlation between the Aβ aggregation and the disease development. Extensive research has been conducted with the aim to reveal the structures of the neurotoxic Aβ aggregates. However, the exact structure of pathological aggregates and mechanism of the disease still remains elusive due to complexity of the occurring processes and instability of various disease-relevant Aβ species. In this article we review up-to-date structural knowledge about amyloid-β peptides, focusing on data acquired using solution and solid state NMR techniques. Furthermore, we discuss implications from these structural studies on the mechanisms of aggregation and neurotoxicity.

AB - Alzheimer's disease (AD) is one of the most prevalent neurodegenerative diseases worldwide. Formation of amyloid plaques consisting of amyloid-β peptides (Aβ) is one of the hallmarks of AD. Several lines of evidence have shown a correlation between the Aβ aggregation and the disease development. Extensive research has been conducted with the aim to reveal the structures of the neurotoxic Aβ aggregates. However, the exact structure of pathological aggregates and mechanism of the disease still remains elusive due to complexity of the occurring processes and instability of various disease-relevant Aβ species. In this article we review up-to-date structural knowledge about amyloid-β peptides, focusing on data acquired using solution and solid state NMR techniques. Furthermore, we discuss implications from these structural studies on the mechanisms of aggregation and neurotoxicity.

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Structural studies of amyloid-β peptides: Unlocking the mechanism of aggregation and the associated toxicity

Abstract

Funding

UN SDGs

Research Areas and Centers

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