lunduniversity.lu.se

Physical Chemistry

Lund University

Denna sida på svenska This page in English

Calendar

Astrid Gräslund: The amyloid β peptide in Alzheimer's disease: molecular interactions and structure conversions studied by chemical and biophysical methods

Seminarium

From: 2018-05-24 18:00 To: 20:30
Place: Kemicentrum, Lecture hall C
Contact: martin.trulsson@teokem.lu.se


Organized by Kemiska föreningen / the Chemichal Society in Lund.

Lecture by Astrid Gräslund, Professor of Biophysics, Stockholm University, Stockholm, Sweden.

Receiver of the Bror Holmberg medal.

 

Abstract:

The amyloid β (Aβ) peptide consists of 39-43 residues and is the major component of the neuritic plaques in the brains of Alzheimer's disease (AD) patients. It is possible to study the peptide self-aggregation process (“amyloid formation”, structures and kinetics) using biophysical methods such as NMR, fluorescence or CD spectroscopy. The interactions of Ab with small molecules, or metal ions such as Zn(II) or Cu(II), that modulate the aggregation process can be studied in semi-stationary states by these methods (1). Kinetic effects on the amyloid formation process can be followed by fluorescence, after labeling the material rich in β-structure by the amyloid-specific dye Thioflavin T. The β-hairpin structure of the peptide with a mainly unstructured N-terminus appears to be a basic unit for formation of the larger amyloid structures associated with insoluble fibrils. Smaller oligomeric peptide aggregates, possibly the major cell toxic agents, can be studied by Soft Ionization Mass Spectrometry. Fluorescence Correlation Spectroscopy (FCS) shows the heterogeneity of the aggregation process of ThT-labeled Aβ in terms of time dependent amyloid aggregate sizes, on a single particle level (2). Modulation of the amyloid formation by Zn(II) or Cu(II) ions binding to specific residues in the N-terminus of the Aβ peptide can be followed by FCS, showing changes in structures as well as kinetics for the aggregation process. Understanding the basic properties, molecular interactions and reactions of the major participants in the chemical processes leading to AD gives a firm basis for the future development of agents that may be used in therapies against AD (3,4). 

 

References: 

1. Abelein, A., Gräslund, A. and Danielsson, J. Zinc as a chaperone-mimicking agent for retardation of amyloid β peptide fibril formation. Proc. Nat. Acad. Sci. US 112 (2015) 5407-5412. 

2. Tiiman, A., Jarvet, J., Gräslund, A. and Vukojevic, V. Heterogeneity and intermediates turnover during amyloid-β (Aβ) peptide aggregation studied by fluorescence correlation spectroscopy. Biochemistry 54 (2015) 7203-7211. 

3. Luo, J., Wärmländer, K.T.S., Gräslund, A. and Abrahams, J.P. Cross interactions between the Alzheimer disease amyloid-β peptide and other amyloid proteins: a further aspect of the amyloid cascade hypothesis. J. Biol. Chem. 291 (2016) 16485-16493. 

4. Wallin, C., Luo, J., Jarvet, J., Wärmländer, K.T.S. and Gräslund, A. The amyloid β peptide in amyloid formation processes: interactions with blood proteins and naturally occurring metal ions. Israel J. Chem. 57 (SI) (2017) 674-685. 

 

Information:

The lecture is open to the public and will be held in English. After the lecture there will be an informal reception at the Centre for Analysis and Synthesis (CAS), where you can meet the lecturer and the other attendants. Pea soup with punsch and pancakes (50 SEK) will be served, as well as other refreshments. 

Register for the reception no later than Monday 21 May by sending an e-mail to anita.hoang 'at' chem.lu.se

 

Find the lecture hall here. Entrance E at Naturvetarvägen 14 will be held open a short time before the lecture for visitors without access-cards.