Brigita Urbanc on Soluble Oligomer Assay Rivals Other Biomarkers in Detecting Preclinical AD

COMMENT The α-sheet secondary structure in oligomers formed by 42 residues long Aβ and α-synuclein, which was shown to correlate with toxicity, is the star of the research reported by Valerie Daggett's group. The observation of the α-sheet, first predicted b

Brigita Urbanc on Distinct thermodynamic signatures of oligomer generation in the aggregation of the amyloid-β peptide.

COMMENT This Nature Chemistry paper by Cohen and collaborators describes a beautiful and thorough study of Aβ-protein fibril formation. The focus is the 42-amino-acids-long alloform Aβ42, which is the most strongly associated with Alzheimer's disease. Aβ42 p

Brigita Urbanc on Amyloid Deposits Not Always Toxic to Cells

COMMENT This paper reports on several important findings derived from a carefully designed study on the VEGFR2 protein. Unlike Aβ-protein or α-synuclein, VEGFR2 does not aggregate in vivo under normal or pathogenic conditions. However, VEGFR2 can be induced to ag

Brigita Urbanc on Electron Microscope Yields Finer Structure of α-Synuclein, Aβ Fibrils

COMMENT In this study, Schmidt and colleagues elucidate the Aβ42 dimer structure within the Aβ42 fibril by cryo-electron microscopy (cryo-EM). This is a follow-up from the previous study of the same group (Schmidt et al., 2009), in which cryo-EM was applied to ex

Brigita Urbanc on Full-length TDP-43 forms toxic amyloid oligomers that are present in frontotemporal lobar dementia-TDP patients.

COMMENT In this comprehensive and multifaceted study, Ruby Chen and her coworkers demonstrated that TDP-43, a protein associated with frontotemporal lobar dementia and amyotrophic lateral sclerosis, assembles into a heterogeneous population of quasispherical and

Brigita Urbanc on Ion mobility-mass spectrometry reveals a conformational conversion from random assembly to β-sheet in amyloid fibril formation.

COMMENT Protein Assembly Pathways Revealed? The question of assembly pathways is central to understanding the formation of protein structures associated with amyloid diseases. The latest research by Bleiholder et al. from the lab of Mike Bowers, recently publishe

Brigita Urbanc on The Toxic Fold? Aβ Dodecamers, Tetramers Show Their Conformations

COMMENT Elusive oligomerization-mediated amyloid-β-protein toxicity: Where have all the trimers gone? Evidence that the pathogenesis of Alzheimer disease (AD) is strongly associated with occurrence of oligomeric assemblies of Aβ is strongly challenging researcher

Brigita Urbanc on Seeded growth of beta-amyloid fibrils from Alzheimer's brain-derived fibrils produces a distinct fibril structure.

COMMENT The pathogenesis of Alzheimer disease (AD) is strongly linked to the amyloid-β protein (Aβ) assembly into amyloid fibrils in the extracellular space, resulting in amyloid plaque deposition. Aβ belongs to the class of amyloid-forming proteins characterized

Brigita Urbanc on A molecular dynamics study of the interaction of D-peptide amyloid inhibitors with their target sequence reveals a potential inhibitory pharmacophore conformation.

COMMENT This is a thorough study that illustrates the importance of molecular dynamics simulations in search for inhibitors of amyloid aggregation. Esteras-Chopo et al. assume a structural model of the fibrillization nuclei of an amyloidogenic amino acid sequence

Brigita Urbanc on Low-power laser irradiation inhibiting Abeta25-35-induced PC12 cell apoptosis via PKC activation.

COMMENT Zhang et al. study inhibition of Aβ25-35-induced PC12 cell apoptosis using low-power laser irradiation. This study is based on an assumption that Aβ25-35 is the critical region that mediated neurotoxicity of full-length Aβ. On the other hand, substantial

Brigita Urbanc on Affibodies—Putting the β in Aβ?

COMMENT Capturing Aβ Using Engineered Affinity Proteins Alzheimer disease (AD) is associated with the amyloid-β protein (Aβ) which assembles into toxic oligomers, protofibrils, and fibrils, and is the major component of amyloid plaques in the AD brain. Substantia

Brigita Urbanc on Systematic in vivo analysis of the intrinsic determinants of amyloid Beta pathogenicity.

COMMENT Aggregation Propensity of Aβ Predicts Longevity of Fly Model of AD AD pathology is strongly associated with initial stages of amyloid-β protein (Aβ) aggregation. At different stages of Aβ assembly, Aβ oligomers, protofibrils, and fibrils are observed whic

Brigita Urbanc on Structural reorganisation and potential toxicity of oligomeric species formed during the assembly of amyloid fibrils.

COMMENT Hydrophobic Residues Exposed to Solvent: A Cause of Oligomer Toxicity? Assembly of proteins into toxic soluble oligomers and highly ordered fibrils is believed to be critical to amyloidogenic diseases associated with protein misfolding and aberrant aggreg

Brigita Urbanc on Linking folding with aggregation in Alzheimer's beta-amyloid peptides.

COMMENT A New Alternative "Endosomic" Amyloid Hypothesis? Amyloid β-protein (Aβ), which is believed to play a critical role at early stages of Alzheimer disease (AD), belongs to the group of natively unfolded proteins. Aβ is known to adopt a collapsed c

Brigita Urbanc on Familial Alzheimer's disease mutations alter the stability of the amyloid beta-protein monomer folding nucleus.

COMMENT Implications of Aβ Folding Stability Alzheimer disease (AD) belongs to a class of diseases associated with protein misfolding and aberrant aggregation. Compelling evidence indicates that initial assembly stages of amyloid-β protein (Aβ), which exists in t