[Abstract Title]. - Society for Neuroscience

Aβ(1-42) in water (100 κM) did not effectively stimulate the cells at a final Aβ concentration of
15 κM. However, continued incubation of the peptide for 48-72 h at 4°C greatly increased TNFα
production which, surprisingly declined upon further incubation of the peptide. Imaging of the
Aβ(1-42) aggregation solutions by atomic force microscopy (AFM) and transmission electron
microscopy (TEM) showed dense globular species immediately upon reconstitution and long
flexible single fibers after continued incubation at 4°C. The appearance of fiber structures
coincided with TNFα production although more concentrated or higher temperature Aβ(1-42)
solutions which showed increased fibrillar content at earlier time points (24 h) were unable to
stimulate the cells. Aβ(1-40) aggregation solutions under similar conditions were unable to
stimulate TNFα production at any aggregation stage . The proinflammatory Aβ(1-42) species
was found to be soluble as centrifugation for 10 mins at 18,000xg did not diminish its ability to
induce TNF-α from THP-1 monocytes. Aβ(1-42) fiber morphology could be regulated by
altering solution conditions. Incubation of the peptide in phosphate-buffered saline (pH 7.1) at
4°C showed a meshwork of loosely-defined fibrillar structures by TEM which failed to evoke a
proinflammatory response compared with incubation in water (pH 3.6). The findings suggest that
an intermediate Aβ(1-42) aggregation species induces the peak proinflammatory response in a
human monocytic cell line.
Disclosures: D. Ajit , None; M.L. Udan, None; M.R. Nichols, None.
Poster
244. Abeta Toxicity I
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 244.10/M3
Topic: C.01.c. Abeta toxicity
Title: Identification and initial characterization of a new binding-partner of the neuroprotective
peptide Humanin
Authors: *A. CARICASOLE 1 , L. ROSSINI 1 , L. TRABALZINI 2 , G. C. TERSTAPPEN 1 ;
1 Siena Biotech, Siena, Italy; 2 Mol. Biol., Univ. of Siena, Siena, Italy
Abstract: Humanin (HN) is a 24-residue peptide able to inhibit neurotoxicity induced by various
insults which can be related to Alzheimer Disease (AD) as well as cell death induced by other
stimuli, but little is known about its biological function in vivo. To date four proteins have been
demonstrated to interact with HN, but none of them has been conclusively demonstrated to be
essential for HN‟s neuroprotective activity. Thus, the identification of new binding partners
and/or regulators of HN is fundamental to understand its physiological function and might also
lead to the identification of novel therapeutic strategies for neurodegenerative disease. We have