Peptides and proteins can convert from their soluble forms into highly ordered fibrillar aggregates, giving rise to pathological conditions ranging from neurodegenerative disorders to systemic amyloidoses. It is increasingly recognized that protein oligomers forming early in the process of fibril aggregation represent the pathogenic species in protein deposition diseases. The N-terminal domain ...

Some amyloid-forming polypeptides are associated with devastating human diseases and others provide important biological functions. For both, oligomeric intermediates appear during amyloid assembly. Currently we have few tools for characterizing these conformationally labile intermediates and discerning what governs their benign versus toxic states. Here, we examine intermediates in the assembl...

α-Synuclein aggregation and accumulation in Lewy bodies are implicated in progressive loss of dopaminergic neurons in Parkinson disease and related disorders. In neurons, the Hsp70s and their Hsp40-like J-domain co-chaperones are the only known components of chaperone network that can use ATP to convert cytotoxic protein aggregates into harmless natively refolded polypeptides. Here we developed...

Burgeoning evidence suggests that soluble oligomers of Abeta (amyloid beta-protein) are the earliest effectors of synaptic compromise in Alzheimer's disease. Whereas most other investigators have employed synthetic Abeta peptides, we have taken advantage of a beta-amyloid precursor protein-overexpressing cell line (referred to as 7PA2) that secretes sub-nanomolar levels of low-n oligomers of Ab...

BACKGROUND Defects in protein folding may lead to severe degenerative diseases characterized by the appearance of amyloid fibril deposits. Cytotoxicity in amyloidoses has been linked to poration of the cell membrane that may involve interactions with amyloid intermediates of annular shape. Although annular oligomers have been detected in many amyloidogenic systems, their universality, function ...

The structural organization of heterogeneous and multiphase natural aggregates depends on the biophysicochemical conditions prevailing in environment, with major ions playing a crucial role. In this study, impact aluminum (Al) iron-organic matter (Fe-OM) was investigated since Al can interact OM be incorporated Fe-oxyhydroxides or adsorbed their surface. Mimetic environmental Fe-OM-Al were synt...

until recently pet scanning has been available only at major universities or teaching hospitals possessing the necessary resources and expertise to operate a research pet facility. most dedicated pet centers cost several millions of dollars, and include a cyclotron, a radiochemistry laboratory to synthesize pet radiopharmaceuticals, a multicrystal dedicated pet camera, advanced computer facilit...

Many neurodegenerative diseases are associated with the self-assembly of peptides and proteins into fibrillar aggregates. Soluble misfolded oligomers formed during aggregation process, or released by mature fibrils, play a relevant role in processes through their interactions neuronal membranes. However, determinants cytotoxicity these still unclear. Here we used liposomes toxic nontoxic same p...

Cyclic hexamers consisting of a 4-octyl, 4-octyloxy and 4-(2-ethylhexyloxy)triphenylamine unit were synthesized via Buchwald-Hartwig cross coupling reaction using A-A, B-B type monomers in order to avoid the formation other cyclic oligomers such as pentamer heptamer. Unlike different size oligomers, all we examined showed clear cold crystallization 165-240°C DSC thermograms. Resulting character...