PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 16515454

Amyloid under the atomic force microscope.

Walraj S Gosal·Sarah L Myers·Sheena E Radford·Neil H Thomson
View original source ↗Export metadata ↓

Abstract

The atomic force microscope (AFM) is a versatile instrument that can be used to image biological samples at nanometre resolution as well as to measure inter and intra-molecular forces in air and liquid environments. This review summarises the use of AFM applied to protein and peptide self-assembly systems involved in amyloid formation. The technical principles of the AFM are outlined and its advantages and disadvantages are highlighted and discussed in the context of the rapidly developing field of amyloid research.

Explore related subjects

Amyloid beta-PeptidesAnimalsForecastingHumansMicroscopy, Atomic ForceJournal ArticleResearch Support, Non-U.S. Gov'tReview

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Walraj S Gosal, Sarah L Myers, Sheena E Radford, Neil H Thomson. 2006. Amyloid under the atomic force microscope.. https://doi.org/10.2174/092986606775338498

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2026

Subcellular proteomic analysis of the DDR2 interactome in a neuronal cell model exposed to Aβ42.

Receptor tyrosine kinases (RTKs) are increasingly understood to signal beyond the plasma membrane. However, the role of Discoidin domain receptor 2 (DDR2), which is activated by collagen, in neurodegeneration remains poorly understood. This study uses immunoprecipitation followed by mass spectrometry on cytoplasmic and nuclear fractions from a neuronal cell model to show that Aβ42 exposure is associated with a compartment-specific reorganization of DDR2-associated protein complexes, characterized by increased nuclear representation. This reveals a unique nuclear DDR2 interactome under amyloidogenic conditions. By exploring this non-canonical, compartment-specific DDR2 signaling pathway, our results offer new insights into how receptor signaling networks may be altered in Alzheimer's disease pathology. Additionally, we identify DDR2-related nuclear interactions as potential sites of dysregulation in neurodegeneration.

Amyloid beta-Peptides↗
PubMed2007

Abeta(25-35) and its C- and/or N-blocked derivatives: copper driven structural features and neurotoxicity.

The toxic properties of beta-amyloid protein, Abeta(1-42), the major component of senile plaques in Alzheimer's disease, depend on nucleation-dependent oligomerization and aggregation. In addition, Abeta(1-42) toxicity is favored by the presence of trace metals, which affect the secondary structure of the peptide. A peptide comprising 11 residues within Abeta(1-42) [Abeta(25-35)] aggregates and retains the neurotoxic activity of Abeta(1-42). We have used both Abeta(25-35) and its C-amidated or N-acetylated/C-amidated derivatives to investigate the role of copper(II) in modulating the conformation and aggregation state as well as the neurotoxic properties of amyloid peptides. Electrospray ionization mass spectrometry (ESI-MS) and electron paramagnetic resonance (EPR) measurements were performed to verify the formation of copper(II)/Abeta(25-35) complexes and to determine the coordination mode, respectively. Abeta(25-35) and its derivatives were analyzed by circular dichroism spectroscopy to assess their secondary structure, subjected to thioflavine-T (Th-T) binding assay to reveal beta-sheet structured aggregates formation, and imaged by scanning force microscopy. Toxicity was assessed on mature cultures of rat cortical neurons. We found that beta-sheet-structured species of Abeta(25-35) were neurotoxic, whereas the random-coil-structured derivatives were devoid of effect. Interestingly, copper promoted the random-coil/beta-sheet transition of Abeta(25-35), with ensuing peptide toxicity, but it induced the toxicity of the N-acetylated/C-amidated derivative without affecting peptide folding. Moreover, copper did not influence either the folding or the activity of the C-amidated Abeta(25-35), suggesting that blockade of the C-terminus of Abeta peptides might be sufficient to prevent Abeta toxicity.

Amyloid beta-Peptides↗
PubMed2007

Glutamatergic synaptic depression by synthetic amyloid beta-peptide in the medial septum.

The medial septum/diagonal band region, which participates in learning and memory processes via its cholinergic and GABAergic projection to the hippocampus, is one of the structures affected by beta amyloid (betaA) deposition in Alzheimer's disease (AD). The acute effects of betaA (25-35 and 1-40) on action potential generation and glutamatergic synaptic transmission in slices of the medial septal area of the rat brain were studied using current and patch-clamp techniques. The betaA mechanism of action through M1 muscarinic receptors and voltage-dependent calcium channels was also addressed. Excitatory evoked responses decreased (30-60%) in amplitude after betaA (2 microM) perfusion in 70% of recorded cells. However, the firing properties were unaltered at the same concentration. This depression was irreversible in most cases, and was not prevented or reversed by nicotine (5 microM). In addition, the results obtained using a paired-pulse protocol support pre- and postsynaptic actions of the peptide. The betaA effect was blocked by calcicludine (50 nM), a selective antagonist of L-type calcium channels, and also by blocking muscarinic receptors with atropine (5 muM) or pirenzepine (1 microM), a more specific M1-receptor blocker. We show that in the medial septal area this oligomeric peptide acts through calcium channels and muscarinic receptors. As blocking any of these pathways blocks the betaA effects, we propose a joint action through both mechanisms. These results may contribute to a better understanding of the pathophysiology at the onset of AD. This understanding will be required for the development of new therapeutic agents.

Amyloid beta-Peptides↗