Nanotechnology for Revealing Molecular Mechanism of Alzheimer’s Disease

Yuri Lyubchenko

Yuri Lyubchenko

Professor, Department of Pharmaceutical Sciences

University of Nebraska

Dr. Lyubchenko’s research falls generally into three large areas:

  • Structural Genomics - DNA Structure, Dynamics and Function;
  • Molecular mechanisms Alzheimer’s, Parkinson’s and similar protein misfolding diseases
  • Nanoimaging - Nanotechnology Applications for Medicine

The structurual genomics projects are centered around chromatin structure and dynamics and DNA recombination and replication. In the chromatin area, we utilized time-lapse AFM to investigate the spontaneous unwrapping of nucleosomes and have proposed a novel model of chromatin dynamics. The recent experiments with the use of a revolutionary high-speed AFM are capable of imaging the dynamics of molecules with video rate, and these have yielded new insights into the pathways of chromatin dynamics. The availability of new AFM methodology is critical for understanding mechanisms of site-specific DNA recombination.

Misfolding and aggregation of proteins are widespread phenomena leading to the development of numerous neurodegenerative disorders such as Parkinson’s, Alzheimer’s, and Huntington’s diseases and there is no cure for any of these devastating protein misfolding diseases. Misfolded states of proteins exist intermittently, so elucidating the mechanism of the formation and the protein aggregation requires the use of methods capable of probing transient conformations of proteins. We developed a novel approach in which misfolded states are probed with AFM force spectroscopy. Using this approach, we were able to identify misfolded states of the protein and characterize their properties. The major finding is that a misfolding dimer has an extremely long lifetime in comparison with the fast conformational dynamics of monomers usually occurring on the microsecond-nanosecond time scale. The high stability of misfolded dimers is a fundamental finding, suggesting that the formation of dimers leads to enormous stabilization of the protein misfolded state. Future studies will provide us with critical information needed for the development of novel and efficient prevention tools, diagnostics and therapeutics for the protein misfolding diseases.

Development of novel nanotechnology for various biomedical applications is an ultimate goal of the research projects under the Nanoimaging program. We developed an entirely novel surface chemistry enabling us to develop one of the most versatile methodologies for AFM imaging. A spin-off from our research has been improvements in the AFM force spectroscopy methodology. There are now rapidly developing and exciting applications of AFM in molecular pharmacology, drug design and other biomedical applications. AFM is capable of direct imaging of molecular dynamics and interactions and we are working on technology development facilitating these studies.

Sponsor & Exhibitor Opportunities

Nanotech Conference & Expo  

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*Sponsorship Opportunities: Contact Chris Erb

Platinum Sponsor

BASF


Nanotech Platinum Sponsor

Chinano

Association Sponsor

Clean Technology and Sustainable Industries Organization (CTSI)

Producing Sponsors

Nano Science and Technology Institute

TechConnect

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*Sponsorship Opportunities: Contact Chris Erb

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