NASA Scientific and Technical Aerospace Reports

20040050760 Parkinson’s Inst., Sunnyvale, CA
Role of Oligomeric a-Synuclein in Mitochondrial Membrane Permeabilization and Neurodegeneration in Parkinson’s
Disease
Lee, Sueng-Jae; Dec. 2003; 27 pp.; In English; Original contains color illustrations
Contract(s)/Grant(s): DAMD17-02-1-0171
Report No.(s): AD-A421068; No Copyright; Avail: CASI; A03, Hardcopy
A growing body of evidence suggests that aggregation of alpha-syn might be the fundamental cause of many
neurodegenerative diseases. Several groups have developed cell culture models to study the cytotoxic effect of alphasynuclein,
and some of them indeed have observed enhanced cell death when alpha-syn, especially its mutant forms, was
overexpressed. However, the link between alpha-syn aggregation and cell death has not been clearly addressed in these model
systems, nor are the molecular mechanisms underlying the toxicity known. We have begun to address these issues in a COS-
7 cell model, and found that alpha-syn aggregation/oligomerization is tightly associated with Golgi fragmentation and cell
death. The fragmentation of the GA has been also confirmed in a neuronal cell model, and the mode of Golgi fragmentation
appears identical to that caused by microtubule-disrupting agents; dispersed Golgi fragments are localized to the transitional
endoplasmic reticulum. These findings indicate that alpha-syn aggregation leads to impairment of microtubule-dependent
intracellular trafficking, which in turn causes Golgi fragmentation.
DTIC
Cells (Biology); Diseases; Membranes; Mitochondria; Nervous System; Oligomers
20040050761 California Univ., Los Angeles, CA
Targeting Angiogenic Factors Contributing to Etiology and Progression of Human Ovarian Cancer
Pietras, Richard J.; Sep. 2003; 11 pp.; In English
Contract(s)/Grant(s): DAMD17-00-1-0558
Report No.(s): AD-A421071; No Copyright; Avail: CASI; A03, Hardcopy
The development of human ovarian cancer depends, in part,,on formation of an adequate blood supply. Tumor
angiogenesis is essential for cancer growth, and vascular endothelial growth factor (VEGF) is critical in stimulating growth
of vascular endothelial cells. VEGF is produced by ovarian cancers, and VEGF secretion is markedly higher in ovarian cancers
with HER-2 oncogene overexpression. Herceptin, an antibody to HER-2 receptors, has direct antitumor effects, but the
antibody also elicits profound reduction in VEGF secretion from ovarian cancer cells, and, thereby, halts tumor- associated
angiogenesis. More complete suppression of angiogenesis may be elicited by treatments that synergistically suppress blood
vessel proliferation, such as squalamine, an angiostatic steroid designated by the FDA as an orphan drug candidate for therapy
of ovarian cancer.
DTIC
Cancer; Etiology
20040050762 Children’s Hospital of Pittsburgh, Pittsburgh, PA
New Advanced Technology to Improve Prediction and Prevention of Type 1 Diabetes
Trucco, Massimo; Nov. 2003; 463 pp.; In English; Original contains color illustrations
Contract(s)/Grant(s): DAMD17-01-1-0009
Report No.(s): AD-A421076; No Copyright; Avail: CASI; A20, Hardcopy
Type 1 diabetes is considered an auto immune disease characterized by the presence of inflammatory cells in the islets
of Langerhas. These cells are T lymphocytes, considered responsible for the destruction of the insulin producing beta-cells
present in the islets. When the majority of the beta cells are dead, the disease presents, frequently with an abrupt and clinically
serious onset. Individuals are considered at high risk to develop the disease, based on their genetic susceptibility (as
determined by the presence of susceptibility alleles at various HLA loci) and on the presence in serum of autoantibodies
directed against islet specific autoantigens (e.g., GAD65, IA-2, and insulin). The aim of this program is to determine whom
among the Army personnel is at high risk to develop the disease in order to prevent the unexpected onset of the disease that
may be associated with tragic consequences, and to initiate an educational program aimed at reducing practical and
psychological hurdles. Furthermore, different individuals develop disease complications (i.e., retinopathy, nephropathy,
neuropathy) at different timepoints after the onset. The susceptibility to complications could also be genetic. The human
genome will be scanned systematically to characterize these susceptibility genes. Proteomic analysis will be performed in
tandem to confirm the genetic associations.
DTIC
Antibodies; Lymphocytes; Metabolic Diseases; Prevention
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