Autophagy, a major degradative pathway for proteins and organelles, is essential for survival of mature neurons. Extensive autophagic-lysosomal pathology in Alzheimer's disease brain contributes to Alzheimer's disease pathogenesis, although the underlying mechanisms are not well understood. Here, we identified and characterized marked intraneuronal amyloid-β peptide/amyloid and lysosomal system...

OBJECTIVE We aimed to describe the natural history of residual insulin secretion in Type 1 Diabetes TrialNet participants over 4 years from diagnosis and relate this to previously reported alternative clinical measures reflecting β-cell secretory function. RESEARCH DESIGN AND METHODS Data from 407 subjects from 5 TrialNet intervention studies were analyzed. All subjects had baseline stimulate...

Zinc is found saturated in the deposited Amyloid-beta ( β A ) peptide plaques in Alzheimer’s disease (AD) patients’ brains. Zinc binding to β A promotes aggregations, including the toxic soluble β A species. Up to now, only the region 1-16 of β A complexed with Zinc ( 16 1− β A -Zn ) is defined structurally in experiment, requiring an efficient theoretical method to present the interaction betw...

Conformational changes of three cyclic β-helical peptides upon adsorption onto planar fused-quartz substrates were detected and analyzed by far-ultraviolet (UV) circular dichroism (CD) spectroscopy. In trifluoroethanol (TFE), hydrophobic peptides, Leu β and Val β, form left- and right-handed helices, respectively, and water-soluble peptide WS β forms a left-handed helix. Upon adsorption, CD spe...

The presence of serum autoantibodies in periodontitis (P) patients against β(1)-adrenoceptor (β(1)-AR), using cardiac membranes or a synthetic β(1)-AR peptide corresponding to the second extracellular loop of human β(1)-AR as antigens, permit us to detect circulating antibody from 40 P patients but not in 20 normal individuals (control). Simultaneously, the P patients exhibited a decrease in HR...

Peptide-based agents derived from well-defined scaffolds offer an alternative to antibodies for selective and high-affinity recognition of large and topologically complex protein surfaces. Here, we describe a strategy for designing oligomers containing both α- and β-amino acid residues ("α/β-peptides") that mimic several peptides derived from the three-helix bundle "Z-domain" scaffold. We show ...

Here we describe a direct access to 2,2,3-trisubstituted syn γ-nitroaldehydes by addition of α-branched aryl acetaldehydes nitroolefins promoted cinchona based squaric acid-derived amino acid peptide. Different α-methyl arylacetaldehydes react with β-aromatic and β-alkyl afford the Michael adducts in high enantioselectivity syn-selectivity. NMR experiments DFT calculations predict reaction occu...

Insertion of an anthranilic acid in an amyloidogenic peptide sequence generates a novel conformationally restricted α/β-hybrid peptide that inhibits amyloid formation of Aβ(1-40) and disrupts preformed fibrillar aggregates in vitro. Such β-sheet breaker hybrid peptides (BSBHps) may be useful for designing novel physiologically important compounds relevant to diverse amyloidoses and for studying...