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20 results on '"Bruggink, Kim A."'

3. Inhibition of α-synuclein aggregation by small heat shock proteins

Author

Bruinsma, Ilona B, Bruggink, Kim A, Kinast, Karsten, Versleijen, Alexandra A M, Segers-Nolten, Ine M J, Subramaniam, Vinod, Kuiperij, H Bea, Boelens, Wilbert, de Waal, Robert M W, Verbeek, Marcel M, and Executive board Vrije Universiteit

Subjects
Microscopy, animal diseases, Research Support, Non-U.S. Gov't, HSP27 Heat-Shock Proteins, Atomic Force, Surface Plasmon Resonance, Small, Research Support, Microscopy, Atomic Force, Protein-Serine-Threonine Kinases, nervous system diseases, Heat-Shock Proteins, Small, nervous system, Mutation, health occupations, alpha-Synuclein, Journal Article, Humans, heterocyclic compounds, Non-U.S. Gov't, Heat-Shock Proteins, Protein Binding
Abstract

The fibrillization of α-synuclein (α-syn) is a key event in the pathogenesis of α-synucleinopathies. Mutant α-syn (A53T, A30P, or E46K), each linked to familial Parkinson's disease, has altered aggregation properties, fibril morphologies, and fibrillization kinetics. Besides α-syn, Lewy bodies also contain several associated proteins including small heat shock proteins (sHsps). Since α-syn accumulates intracellularly, molecular chaperones like sHsps may regulate α-syn folding and aggregation. Therefore, we investigated if the sHsps αB-crystallin, Hsp27, Hsp20, HspB8, and HspB2B3 bind to α-syn and affect α-syn aggregation. We demonstrate that all sHsps bind to the various α-syns, although the binding kinetics suggests a weak and transient interaction only. Despite this transient interaction, the various sHsps inhibited mature α-syn fibril formation as shown by a Thioflavin T assay and atomic force microscopy. Interestingly, HspB8 was the most potent sHsp in inhibiting mature fibril formation of both wild-type and mutant α-syn. In conclusion, sHsps may regulate α-syn aggregation and, therefore, optimization of the interaction between sHsps and α-syn may be an interesting target for therapeutic intervention in the pathogenesis of α-synucleinopathies.

Published
2011

16. The Diagnostic Value of CSF Amyloid-43 in Differentiation of Dementia Syndromes

Author

A. Bruggink, Kim, Bea Kuiperij, H., A.H.R. Claassen, Jurgen, and M. Verbeek, Marcel

Abstract

Amyloid- (A) is known as the most prominent core protein in Alzheimers Disease (AD) senile plaques. Although research has focused mainly on A40 and A42 as potential cerebrospinal fluid (CSF) biomarkers, a range of A peptides with variable lengths has been demonstrated in the brains and CSF of AD patients. Recently, it has been found that the A43 peptide may be more abundant than previously assumed, could therefore play an important role in AD pathophysiology, and hence also function as putative biomarker. In this study the value of CSF A43 in AD diagnosis was investigated. A43 levels in CSF were highly correlated with A42 levels. Furthermore, in differentiation of AD from nondemented controls and from patients with Lewy body dementia and frontotemporal dementia, A43 had an equal diagnostic value as A42, both as a single biomarker and in combination with total and phosphorylated tau. In conclusion, quantification of A43 in CSF does not add novel diagnostic information to the differential diagnosis of AD compared to existing biomarkers.

Published
2013

20. Inhibition of α-synuclein aggregation by small heat shock proteins.

Author

Bruinsma IB, Bruggink KA, Kinast K, Versleijen AA, Segers-Nolten IM, Subramaniam V, Kuiperij HB, Boelens W, de Waal RM, and Verbeek MM

Subjects
HSP27 Heat-Shock Proteins metabolism, Heat-Shock Proteins metabolism, Humans, Microscopy, Atomic Force, Molecular Chaperones, Mutation, Protein Binding, Protein Serine-Threonine Kinases metabolism, Surface Plasmon Resonance, alpha-Synuclein genetics, Heat-Shock Proteins, Small metabolism, alpha-Synuclein metabolism
Abstract

The fibrillization of α-synuclein (α-syn) is a key event in the pathogenesis of α-synucleinopathies. Mutant α-syn (A53T, A30P, or E46K), each linked to familial Parkinson's disease, has altered aggregation properties, fibril morphologies, and fibrillization kinetics. Besides α-syn, Lewy bodies also contain several associated proteins including small heat shock proteins (sHsps). Since α-syn accumulates intracellularly, molecular chaperones like sHsps may regulate α-syn folding and aggregation. Therefore, we investigated if the sHsps αB-crystallin, Hsp27, Hsp20, HspB8, and HspB2B3 bind to α-syn and affect α-syn aggregation. We demonstrate that all sHsps bind to the various α-syns, although the binding kinetics suggests a weak and transient interaction only. Despite this transient interaction, the various sHsps inhibited mature α-syn fibril formation as shown by a Thioflavin T assay and atomic force microscopy. Interestingly, HspB8 was the most potent sHsp in inhibiting mature fibril formation of both wild-type and mutant α-syn. In conclusion, sHsps may regulate α-syn aggregation and, therefore, optimization of the interaction between sHsps and α-syn may be an interesting target for therapeutic intervention in the pathogenesis of α-synucleinopathies., (Copyright © 2011 Wiley-Liss, Inc.)

Published
2011
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