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Depression is one of the most common psychiatric symptoms in Alzheimer's disease (AD), and considerable evidence indicates that major depressive disorder increases the risk of AD. 1–3 To date, however, the molecular mechanisms underlying the clinical association between depression and AD have remained elusive. Soluble oligomers of the amyloid-b peptide(More)
The main hypothesis for prion diseases proposes that the cellular protein (PrP(C)) can be altered into a misfolded, beta-sheet-rich isoform (PrP(Sc)), which in most cases undergoes aggregation. In an organism infected with PrP(Sc), PrP(C) is converted into the beta-sheet form, generating more PrP(Sc). We find that sequence-specific DNA binding to(More)
The infectious agent of transmissible spongiform encephalopathies (TSE) is believed to comprise, at least in part, the prion protein (PrP). Other molecules can modulate the conversion of the normal PrP(C) into the pathological conformer (PrP(Sc)), but the identity and mechanisms of action of the key physiological factors remain unclear. PrP can bind to(More)
Parkinson's disease (PD) is characterized by the presence of cytoplasmic inclusions composed of alpha-synuclein (alpha-syn) in dopaminergic neurons. This suggests a pivotal role of dopamine (DA) on PD development. Here, we show that DA modulates differently the stability of protofibrils (PF) and fibrils (F) composed of wild type or variants of alpha-syn(More)
We investigated the mechanisms of anticoagulant activity mediated by sulfated galactans. The anticoagulant activity of sulfated polysaccharides is achieved mainly through potentiation of plasma cofactors, which are the natural inhibitors of coagulation proteases. Our results indicated the following. 1) Structural requirements for the interaction of sulfated(More)
Bacteriophage P22 is a double-stranded DNA containing phage. Its morphogenetic pathway requires the formation of a precursor procapsid that subsequently matures to the capsid. The stability of bacteriophage P22 coat protein in both monomeric and polymeric forms under hydrostatic pressure has been examined previously [Prevelige, P. E., King, J., & Silva, J.(More)
Cooperativity in the interactions among proteins subunits and DNA is crucial for DNA recognition. LexA repressor was originally thought to bind DNA as a monomer, with cooperativity leading to tighter binding of the second monomer. The main support for this model was a high value of the dissociation constant for the LexA dimer (micromolar range). Here we(More)
Recent studies on the effect of pressure on macromolecular assemblages have provided new information on protein-protein and protein-nucleic acid interactions. New findings have recently emerged on the use of hydrostatic pressure to assess intermediate states in the assembly pathways of viruses, multimeric proteins and protein-nucleic acid complexes,(More)
Hydrostatic pressure is a powerful tool for studying protein folding, and the dynamics and structure of folding intermediates. Recently, pressure techniques have opened two important fronts to aid our understanding of how polypeptides fold into highly structured conformations. The first advance is the stabilization of folding intermediates, making it(More)
Misfolding and misassembly of proteins are major problems in the biotechnology industry, in biochemical research, and in human disease. Here we describe a novel approach for reversing aggregation and increasing refolding by application of hydrostatic pressure. Using P22 tailspike protein as a model system, intermediates along the aggregation pathway were(More)