Patrick Flagmeier
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View article: N-Terminal Acetylation of α-Synuclein Slows down Its Aggregation Process and Alters the Morphology of the Resulting Aggregates
N-Terminal Acetylation of α-Synuclein Slows down Its Aggregation Process and Alters the Morphology of the Resulting Aggregates Open
Parkinson's disease is associated with the aberrant aggregation of α-synuclein. Although the causes of this process are still unclear, post-translational modifications of α-synuclein are likely to play a modulatory role. Since α-synuclein …
View article: Squalamine and Its Derivatives Modulate the Aggregation of Amyloid-β and α-Synuclein and Suppress the Toxicity of Their Oligomers
Squalamine and Its Derivatives Modulate the Aggregation of Amyloid-β and α-Synuclein and Suppress the Toxicity of Their Oligomers Open
The aberrant aggregation of proteins is a key molecular event in the development and progression of a wide range of neurodegenerative disorders. We have shown previously that squalamine and trodusquemine, two natural products in the aminos…
View article: Wild-type sTREM2 blocks Aβ aggregation and neurotoxicity, but the Alzheimer's R47H mutant increases Aβ aggregation
Wild-type sTREM2 blocks Aβ aggregation and neurotoxicity, but the Alzheimer's R47H mutant increases Aβ aggregation Open
TREM2 is a pattern recognition receptor, expressed on microglia and myeloid cells, detecting lipids andAβ and inducing an innate immune response. Missense mutations (e.g., R47H) of TREM2 increase risk of Alzheimer’s disease (AD). The solub…
View article: Comparative Studies in the A30P and A53T α-Synuclein C. elegans Strains to Investigate the Molecular Origins of Parkinson's Disease
Comparative Studies in the A30P and A53T α-Synuclein C. elegans Strains to Investigate the Molecular Origins of Parkinson's Disease Open
The aggregation of α-synuclein is a hallmark of Parkinson's disease (PD) and a variety of related neurological disorders. A number of mutations in this protein, including A30P and A53T, are associated with familial forms of the disease. Pa…
View article: Elongation rate and average length of amyloid fibrils in solution using isotope-labelled small-angle neutron scattering
Elongation rate and average length of amyloid fibrils in solution using isotope-labelled small-angle neutron scattering Open
We demonstrate a solution method that allows both elongation rate and average length of amyloid fibrils to be independently determined.
View article: Wild-type sTREM2 blocks Aβ aggregation and neurotoxicity, but the Alzheimer's R47H mutant increases Aβ aggregation
Wild-type sTREM2 blocks Aβ aggregation and neurotoxicity, but the Alzheimer's R47H mutant increases Aβ aggregation Open
View article: Screening of small molecules using the inhibition of oligomer formation in α-synuclein aggregation as a selection parameter
Screening of small molecules using the inhibition of oligomer formation in α-synuclein aggregation as a selection parameter Open
View article: Wild-type sTREM2 blocks Aβ aggregation and neurotoxicity, while the Alzheimer’s R47H mutant does the opposite
Wild-type sTREM2 blocks Aβ aggregation and neurotoxicity, while the Alzheimer’s R47H mutant does the opposite Open
Missense mutations (e.g. R47H) of the microglial receptor TREM2 increase risk of Alzheimer’s disease (AD), and the soluble ectodomain of wild-type TREM2 (sTREM2) appears to protect in vivo, but the underlying mechanisms are unclear. We sho…
View article: The Influence of Pathogenic Mutations in α-Synuclein on Biophysical and Structural Characteristics of Amyloid Fibrils
The Influence of Pathogenic Mutations in α-Synuclein on Biophysical and Structural Characteristics of Amyloid Fibrils Open
Proteinaceous deposits of α-synuclein amyloid fibrils are a hallmark of human disorders including Parkinson's disease. The onset of this disease is also associated with five familial mutations of the gene encoding the protein. However, the…
View article: An engineered monomer binding-protein for α-synuclein efficiently inhibits the proliferation of amyloid fibrils
An engineered monomer binding-protein for α-synuclein efficiently inhibits the proliferation of amyloid fibrils Open
Removing or preventing the formation of -synuclein aggregates is a plausible strategy against Parkinson’s disease. To this end, we have engineered the -wrapin AS69 to bind monomeric -synuclein with high affinity. In cultured cells, A…
View article: Author response: An engineered monomer binding-protein for α-synuclein efficiently inhibits the proliferation of amyloid fibrils
Author response: An engineered monomer binding-protein for α-synuclein efficiently inhibits the proliferation of amyloid fibrils Open
Article Figures and data Abstract Introduction Results Discussion Materials and methods Appendix 1 Appendix 2 Appendix 3 Data availability References Decision letter Author response Article and author information Metrics Abstract Removing …
View article: Author response: An engineered monomer binding-protein for α-synuclein efficiently inhibits the proliferation of amyloid fibrils
Author response: An engineered monomer binding-protein for α-synuclein efficiently inhibits the proliferation of amyloid fibrils Open
Article Figures and data Abstract Introduction Results Discussion Materials and methods Appendix 1 Appendix 2 Appendix 3 Data availability References Decision letter Author response Article and author information Metrics Abstract Removing …
View article: Different soluble aggregates of Aβ42 can give rise to cellular toxicity through different mechanisms
Different soluble aggregates of Aβ42 can give rise to cellular toxicity through different mechanisms Open
View article: An engineered monomer binding-protein for<i>α</i>-synuclein efficiently inhibits the proliferation of amyloid fibrils
An engineered monomer binding-protein for<i>α</i>-synuclein efficiently inhibits the proliferation of amyloid fibrils Open
Removing or preventing the formation of α -synuclein aggregates is a plausible strategy against Parkinson’s disease. To this end we have engineered the β -wrapin AS69 to bind monomeric α -synuclein with high affinity. In cultured cells, AS…
View article: Mapping Surface Hydrophobicity of α-Synuclein Oligomers at the Nanoscale
Mapping Surface Hydrophobicity of α-Synuclein Oligomers at the Nanoscale Open
Proteins fold into a single structural ensemble but can also misfold into many diverse structures including small aggregates and fibrils, which differ in their toxicity. The aggregate surface properties play an important role in how they i…
View article: Quantifying Co-Oligomer Formation by α-Synuclein
Quantifying Co-Oligomer Formation by α-Synuclein Open
Small oligomers of the protein α-synuclein (αS) are highly cytotoxic species associated with Parkinson's disease (PD). In addition, αS can form co-aggregates with its mutational variants and with other proteins such as amyloid-β (Aβ) and t…
View article: Nanoscopic Characterisation of Individual Endogenous Protein Aggregates in Human Neuronal Cells
Nanoscopic Characterisation of Individual Endogenous Protein Aggregates in Human Neuronal Cells Open
The aberrant misfolding and subsequent conversion of monomeric protein into amyloid aggregates characterises many neurodegenerative disorders, including Parkinson's and Alzheimer's diseases. These aggregates are highly heterogeneous in str…
View article: Multistep Inhibition of α-Synuclein Aggregation and Toxicity <i>in Vitro</i> and <i>in Vivo</i> by Trodusquemine
Multistep Inhibition of α-Synuclein Aggregation and Toxicity <i>in Vitro</i> and <i>in Vivo</i> by Trodusquemine Open
The aggregation of α-synuclein, an intrinsically disordered protein that is highly abundant in neurons, is closely associated with the onset and progression of Parkinson's disease. We have shown previously that the aminosterol squalamine c…
View article: Single-Molecule Characterization of the Interactions between Extracellular Chaperones and Toxic α-Synuclein Oligomers
Single-Molecule Characterization of the Interactions between Extracellular Chaperones and Toxic α-Synuclein Oligomers Open
View article: Systematic Development of Small Molecules to Inhibit Specific Steps of α-Synuclein Aggregation in Parkinson's Disease
Systematic Development of Small Molecules to Inhibit Specific Steps of α-Synuclein Aggregation in Parkinson's Disease Open
View article: Optical Structural Analysis of Individual α‐Synuclein Oligomers
Optical Structural Analysis of Individual α‐Synuclein Oligomers Open
Small aggregates of misfolded proteins play a key role in neurodegenerative disorders. Such species have proved difficult to study due to the lack of suitable methods capable of resolving these heterogeneous aggregates, which are smaller t…
View article: Optical Structural Analysis of Individual α‐Synuclein Oligomers
Optical Structural Analysis of Individual α‐Synuclein Oligomers Open
Small aggregates of misfolded proteins play a key role in neurodegenerative disorders. Such species have proved difficult to study due to the lack of suitable methods capable of resolving these heterogeneous aggregates, which are smaller t…
View article: Hsp70 Inhibits the Nucleation and Elongation of Tau and Sequesters Tau Aggregates with High Affinity
Hsp70 Inhibits the Nucleation and Elongation of Tau and Sequesters Tau Aggregates with High Affinity Open
As a key player of the protein quality control network of the cell, the molecular chaperone Hsp70 inhibits the aggregation of the amyloid protein tau. To date, the mechanism of this inhibition and the tau species targeted by Hsp70 remain u…
View article: Inhibiting the Ca2+ Influx Induced by Human CSF
Inhibiting the Ca2+ Influx Induced by Human CSF Open
View article: An interdisciplinary approach to studying mechanistic, structural and toxic features of protein aggregates associated with neurodegenerative disorders.
An interdisciplinary approach to studying mechanistic, structural and toxic features of protein aggregates associated with neurodegenerative disorders. Open
The misfolding and aggregation of proteins is closely associated with more than fifty human disorders, including Alzheimer's and Parkinson's diseases, all of which are currently incurable and many represent a major threat to human life. Th…
View article: Ultrasensitive Measurement of Ca<sup>2+</sup> Influx into Lipid Vesicles Induced by Protein Aggregates
Ultrasensitive Measurement of Ca<sup>2+</sup> Influx into Lipid Vesicles Induced by Protein Aggregates Open
To quantify and characterize the potentially toxic protein aggregates associated with neurodegenerative diseases, a high‐throughput assay based on measuring the extent of aggregate‐induced Ca 2+ entry into individual lipid vesicles has bee…
View article: A natural product inhibits the initiation of α-synuclein aggregation and suppresses its toxicity
A natural product inhibits the initiation of α-synuclein aggregation and suppresses its toxicity Open
Significance Parkinson’s disease is characterized by the presence in brain tissues of aberrant aggregates primarily formed by the protein α-synuclein. It has been difficult, however, to identify compounds capable of preventing the formatio…
View article: β-Synuclein suppresses both the initiation and amplification steps of α-synuclein aggregation via competitive binding to surfaces
β-Synuclein suppresses both the initiation and amplification steps of α-synuclein aggregation via competitive binding to surfaces Open
View article: Mutations associated with familial Parkinson’s disease alter the initiation and amplification steps of α-synuclein aggregation
Mutations associated with familial Parkinson’s disease alter the initiation and amplification steps of α-synuclein aggregation Open
Significance Proteinaceous deposits composed primarily of amyloid fibrils of α-synuclein are a hallmark of a range of neurological disorders including Parkinson’s disease. Mutations of the gene encoding α-synuclein have been associated wit…
View article: Chemical properties of lipids strongly affect the kinetics of the membrane-induced aggregation of α-synuclein
Chemical properties of lipids strongly affect the kinetics of the membrane-induced aggregation of α-synuclein Open
Significance Parkinson’s disease is the second most prevalent neurodegenerative disorder and is characterized by the presence in the brains of patients of proteinaceous deposits whose main component is α-synuclein. This protein interacts w…