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NANO-TECHNOLOGY-BASED APPROACH FOR POTENTIAL THERAPY OF NEURODEGENERATIVE DISEASES (NDD) |
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Prof. Shlomo Margel: Department of Chemistry, Bar-Ilan University, Ramat Gan
“This BSF grant has broadened my research scope in NDD. Since my mother passed away from AD (Alzheimer’s Disease), this has become an important issue for me personally.”
Prof. Georges Belfort: Howard P. Isermann Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, New York
“This BSF grant has helped me partially support my Post-Doctoral Researcher, Dr. Mirco Sorcci and pay for the research before and during the visit of Hadas Skaat, a student from Bar Ilan University.”
It is now 100 years since the first report of AD (Alzheimer’s Disease): pre-senile dementia associated with diffuse cortical atrophy, nerve cell loss, plaques and tangles. In the last few years, scientists using various state-of-the-art molecular approaches have come to realize that AD is much more closely related than previously thought to various other degenerative conditions, including PD (Parkinson’s Disease), type 2 diabetes and Creutzfeldt-Jakob Disease (the human version of Mad Cow Disease). A hallmark of all these disorders is formation of insoluble extracellular fibrils (rich in β-sheet structure) from proteins that are normally soluble.
Profs. Margel and Belfort are now testing various nano-particles that interfere with β-A (β-amyloid) fibril formation in AD and other conditions at various stages, which they also plan to evaluate using a neurological cell assay. Their eventual aim is to use their findings to develop novel therapeutic approaches for diseases characterized by β-A fibril formation.
Cooperation .Pofs. Margel and Belfort combine nano-technological and bio-technological approaches. Prof. Margel’s group at Bar-Ilan University synthesized several magnetic nano-particles of various sizes and with different surface characteristics (hydrophilic and hydrophobic properties). Prof. Belfort’s group at the Rensselaer Polytechnic Institute tested these nano-particles using the insulin amyloid assay they developed.
Findings The typical fibril formation process is characterized by three phases: 1. The lag phase, in which the nucleation process occurs but fibers are not detectable. 2. The elongation/broadening phase, during which formation of fiber of various diameters and lengths begin. 3. The saturation phase, during which most of the soluble proteins are converted into fibrils.
These phases are affected by various conditions, such as initial protein concentration, pH, ionic strength, presence of “seeding” centers, foreign surfaces, and the intensity of agitation. For example, for human insulin at pH 1.6 and 65ºC, phase 1 is about 3 hours and phase 2 up to 2 hours. The addition of nano-particles (g-Fe2O3/poly(1H, 1H-heptafluorobutylacrylate) significantly extends phase 1 to 20 hours as well as slowing down fibril growth.
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Kinetics of Fibril Formation |
