An antibody scanning method for the detection of α-synuclein oligomers in the serum of Parkinson's disease patients.

Misfolded α-synuclein oligomers are closely implicated in the pathology of Parkinson's disease and related synucleinopathies. The elusive nature of these aberrant assemblies makes it challenging to develop quantitative methods to detect them and modify their behavior. Existing detection methods use antibodies to bind α-synuclein aggregates in biofluids, although it remains challenging to raise antibodies against α-synuclein oligomers.

Structure-specific amyloid precipitation in biofluids.

The composition of soluble toxic protein aggregates formed in vivo is currently unknown in neurodegenerative diseases, due to their ultra-low concentration in human biofluids and their high degree of heterogeneity. Here we report a method to capture amyloid-containing aggregates in human biofluids in an unbiased way, a process we name amyloid precipitation. We use a structure-specific chemical dimer, a Y-shaped, bio-inspired small molecule with two capture groups, for amyloid precipitation to increase affinity.

Mapping the binding site topology of amyloid protein aggregates using multivalent ligands.

A key process in the development of neurodegenerative diseases such as Alzheimer's and Parkinson's diseases is the aggregation of proteins to produce fibrillary aggregates with a cross β-sheet structure, amyloid. The development of reagents that can bind these aggregates with high affinity and selectivity has potential for early disease diagnosis. By linking two benzothiazole aniline (BTA) head groups with different length polyethylene glycol (PEG) spacers, fluorescent probes that bind amyloid fibrils with low nanomolar affinity have been obtained.

Quantifying misfolded protein oligomers as drug targets and biomarkers in Alzheimer and Parkinson diseases.

Protein misfolding and aggregation are characteristic of a wide range of neurodegenerative disorders, including Alzheimer and Parkinson diseases. A hallmark of these diseases is the aggregation of otherwise soluble and functional proteins into amyloid aggregates. Although for many decades such amyloid deposits have been thought to be responsible for disease progression, it is now increasingly recognized that the misfolded protein oligomers formed during aggregation are, instead, the main agents causing pathological processes.

The Costs of Close Contacts: Visualizing the Energy Landscape of Cell Contacts at the Nanoscale.

Cell-cell contacts often underpin signaling between cells. For immunology, the binding of a T cell receptor to an antigen-presenting pMHC initiates downstream signaling and an immune response. Although this contact is mediated by proteins on both cells creating interfaces with gap sizes typically around 14 nm, many, often contradictory observations have been made regarding the influence of the contact on parameters such as the binding kinetics, spatial distribution, and diffusion of signaling proteins within the contact.