Search results for " oligomer"

Trifluoroethanol modulates α-synuclein amyloid-like aggregate formation, stability and dissolution

2016

The conversion of proteins into amyloid fibrils and other amyloid-like aggregates is closely connected to the onset of a series of age-related pathologies. Upon changes in environmental conditions, amyloid-like aggregates may also undergo disassembly into oligomeric aggregates, the latter being recognized as key effectors in toxicity. This indicates new possible routes for in vivo accumulation of toxic species. In the light of the recognized implication of α-Synuclein (αSN) in Parkinson's disease, we present an experimental study on supramolecular assembly of αSN with a focus on stability and disassembly paths of such supramolecular aggregate species. Using spectroscopic techniques, two-pho…

Proinflammatory and amyloidogenic S100A9 induced by traumatic brain injury in mouse model.

2019

Traumatic brain injury (TBI) represents a significant risk factor for development of neurodegenerative diseases such as Alzheimer’s and Parkinson’s. The S100A9-driven amyloid-neuroinflammatory cascade occurring during primary and secondary TBI events can serve as a mechanistic link between TBI and Alzheimer’s as demonstrated recently in the human brain tissues. Here by using immunohistochemistry in the controlled cortical impact TBI mouse model we have found pro-inflammatory S100A9 in the brain tissues of all mice on the first and third post-TBI days, while 70% of mice did not show any S100A9 presence on seventh post-TBI day similar to controls. This indicates that defensive mechanisms effe…

Modulating disease-relevant tau oligomeric strains by small molecules

2020

The pathological aggregation of tau plays an important role in Alzheimer's disease and many other related neurodegenerative diseases, collectively referred to as tauopathies. Recent evidence has demonstrated that tau oligomers, small and soluble prefibrillar aggregates, are highly toxic due to their strong ability to seed tau misfolding and propagate the pathology seen across different neurodegenerative diseases. We previously showed that novel curcumin derivatives affect preformed tau oligomer aggregation pathways by promoting the formation of more aggregated and nontoxic tau aggregates. To further investigate their therapeutic potential, we have extended our studies o disease-relevant bra…

Preselection of cases through expert clinical and radiological review significantly increases mutation detection rate in multiple epiphyseal dysplasia

2006

Skeletal dysplasias are difficult to diagnose for the nonexpert. In a previous study of patients with multiple epiphyseal dysplasia (MED), we identified cartilage oligomeric matrix protein (COMP) mutations in only 36% of cases and suspected that the low-mutation detection rate was partially due to misdiagnosis. We therefore instituted a clinical–radiographic review system, whereby all cases were evaluated by a panel of skeletal dysplasia experts (European Skeletal Dysplasia Network). Only those patients in whom the diagnosis of MED was confirmed by the panel were screened for mutations. Under this regimen the mutation detection rate increased to 81%. When clinical–radiological diagnostic cr…

Atmospheric protein chemistry influenced by anthropogenic air pollutants: nitration and oligomerization upon exposure to ozone and nitrogen dioxide

2017

The allergenic potential of airborne proteins may be enhanced via post-translational modification induced by air pollutants like ozone (O3) and nitrogen dioxide (NO2). The molecular mechanisms and kinetics of the chemical modifications that enhance the allergenicity of proteins, however, are still not fully understood. Here, protein tyrosine nitration and oligomerization upon simultaneous exposure of O3 and NO2 were studied in coated-wall flow-tube and bulk solution experiments under varying atmospherically relevant conditions (5–200 ppb O3, 5–200 ppb NO2, 45–96% RH), using bovine serum albumin as a model protein. Generally, more tyrosine residues were found to react via the nitration pathw…

Input of P, N-(phosphanyl, amino)-ferrocene hybrid derivatives in late transition metals catalysis

2018

International audience; Unequally functionalized ferrocenes give access to valuable hemilabile reactivity in catalytic reaction. We address the synthesis of hybrid (P, N)-ferrocenyl compounds for which recent catalytic breakthrough applications have been reported, transversely in late transition metals chemistry. Palladium, nickel, rhodium, iridium, and emerging iron and gold catalysis are illustrated from selected examples, which include CC bond formation from cross-coupling and polymerization, allylic substitution, cyanation, hydroformylation, CH arylation and silylation and hydrogenation reactions.

CHARACTERIZATION OF THE SYNAPTIC PROTEOME IN NON-DEMENTED SUBJECTS WITH ALZHEIMER’S NEUROPATHOLOGY

Some individuals, here refereed to as Non-Demented with Alzheimer’s Neuropathology (NDAN), retain their congitive function despite the presence of amyloid plaques and tau tangles typical of symptomatic Alzheimer’s Disease (AD). In NDAN, unlike AD, toxic amyloid beta oligomers do not localize to the postsynaptic densities (PSDs). Synaptic resistance to amyloid beta in NDAN may thus enable these individuals to remain cognitively intact despite the AD-like pathology. The mechanim(s) responsible for this resistance remains unresolved and understanding such protective biological processes could reveal novel targets for the development of effective treatments for AD. The current work describes th…

Near infrared light to promote synaptic resilience to Alzheimer’s Disease neuropathology

Alzheimer’s Disease (AD) is a multifactorial neurodegenerative dementia with no curative therapeutic options. One of the earliest impairments in AD triggering cognitive decline is the synaptic dysfunction induced by the selective targeting and interruption of the synaptic region by the small oligomeric form of amyloid beta (Aβ). Recently, the co-presence of Aβ oligomers (Aβo) and tau oligomers (tau-o) at the synapses has been suggested to exacerbate this dysfunction. Therefore, the development of therapeutics aimed at protecting the synapses from the toxic binding of both proteins at the synapses can preserve synaptic health and cognitive function. With this goal in mind, the present study …

Concentration dependence of amplified spontaneous emission in two oligo-(p-phenylenevinylene) derivatives

2005

Amplified spontaneous emission sASEd in optically pumped polystyrene sPSd films doped with two different oligo-sp-phenylenevinylened derivatives sOPVsd, with three s3-OPVd and five s5-OPVd monomer units is reported. It is observed that there is a maximum content of oligomer s25 wt. % for 3-OPV and 20 wt. % for 5-OPVd that can be introduced in the films, due to degradation sin 3-OPVd and ASE quenching sin 5-OPVd. Optimal concentrations swith minimum pump-intensity thresholds for the observation of ASEd of 15 wt. % and 9 wt. % are measured for the trimer and the pentamer, respectively. The concentration dependence of the ASE threshold is discussed in terms of the optical absorption spectra. G…

Concanavalin A aggregation and toxicity on cell cultures

2009

A number of neurodegenerative diseases are known to involve protein aggregation. Common mechanisms and structural properties of amyloids are thought to be involved in aggregation-related cytotoxicity. In this context we propose an experimental study on Concanavalin A (Con A) aggregation and use it as a model to study the relationship between cell toxicity and aggregation processes. Depending on solution conditions, Con A aggregation has been monitored by static and dynamic light scattering, Thioflavin T emission, and FTIR absorption. The morphology of different aggregate species was verified by means of Atomic Force Microscopy and Confocal Microscopy. During the aggregation pathway the nati…