Cindy S. Orser

Detection of misfolded prion protein in blood with conformationally sensitive peptides

BACKGROUND: The long‐standing goal of a preclinical diagnostic test for transmissible spongiform encephalopathy (TSE) has recently become urgent because of the discovery that humans with variant Creutzfeldt‐Jakob disease can transmit disease via blood transfusions.

Wound‐healing properties of trehalose‐stabilized freeze‐dried outdated platelets

BACKGROUND: The wound‐healing applications of platelet (PLT)‐derived cytokines, proteins, and membranes is accepted but continues to be investigated. In this study, it is demonstrated that stabilized freeze‐dried PLTs prepared from outdated PLTs (FDPOs) accelerate wound healing and form tube structures as well as stabilized indated freeze‐dried PLTs (FDPIs) and room‐temperature fresh PLTs (RT‐PLTs).

P-060: Abeta pronucleon diagnostic peptides with application for RX-DX screening

Novel peptides that mimic conformationally unique regions of target amyloid proteins associated with neurodegenerative diseases such as Alzheimer’s disease have been designed. The peptide ligands, called Pronucleon peptides, undergo a conformational change from alpha helix to -sheet upon binding of disease-associated target amyloid proteins. Conformational change, observed by circular dichroism, can be followed through engineered fluorophores conjugated to the termini of the peptide that form excimers when induced to -sheet by the presence of the target protein. Immobilized Pronucleon peptides have been shown to compete with A 42 for A 40 monomers in binding studies, suggesting that they can be directly recruited to A eta disease-associated molecules. Because the Pronucleon peptides form a direct interaction with the target substrate, they have dual utility as both a diagnostic screen for A eta conformation and Alzheimer’s disease as well as for use in a drug-screening assay. Pronucleon peptide assay reactions with clinical cerebrospinal fluid from confirmed AD cases and from age matched cognitive normal adults, conducted in a 96-well plate format using a TECAN scanning spectrofluorometer, were able to distinguish the two groups. Known A eta aggregate effector compounds have been evaluated in the same rapid microtiter plate assay format with results mimicking much more complex and time consuming bioassays.