Non-Ionizing Electromagnetic Radiation Impact on Protein Misfolding and Neurodegenerative Diseases

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Terahertz (THz or TH) band is non-ionizing electromagnetic radiation (NIER) lying between microwave and infrared rays wavelengths. TH radiation is useful in medical diagnostics, petrochemical, aerospace industries, security and scientific research. In medical field, TH radiation sensitivity to the molecular properties of biological tissue, from cell hydration to conformation states of important biomolecules, has spurred development of new TH-based approaches to cancer diagnosis. TH pulsed imaging was demonstrated to succeed in detection of breast cancer, melanoma and basal cell skin carcinoma. The first in vivo trials of TH imaging as an intra-operative tool during cancer surgery are currently underway. The TH spectral region of 0.1-10 THz NIER has been demonstrated to have a great potential as diagnostic and treatment tool in different fields of medicine. On the physical level, energy delivered by TH waves induces atoms’ vibrations, incapable to degrade biomacromolecules, such as nucleic acids and proteins. However, theoretical research suggests that picosecond TH pulses may enhance hydrogen bonds vibrations leading to openings between the DNA strands, subsequently triggering an increase in the multiple tumor suppressor proteins levels, ceasing cell-cycle progression. This strategy could be beneficial in ceasing of tumorogenesis and subsequently in cancer therapy. Moreover, TH waves exhibit a potential affecting protein folding dynamics, deterioration of which is the major hallmark of a wide range of diseases, particularly of the most neurodegenerative diseases.

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In our Laboratory

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The project is at the initial stage. The project is conducted in collaboration and under sponsorship of the National Institute for Translational Research at Ariel University. 

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Plans

Here we relied on our hypothesis suggesting that specific energy density of terahertz non-ionizing electromagnetic radiation is capable to alter secondary and tertiary structures of DNA and protein molecule; these alterations, in turn, will leads to 1) disintegration of double strand DNA molecule necessary for activation cell tumor suppressor mechanisms and 2) overcome kinetically unfavorable state of global minimum allowing disintegration of aggregated protein fibrils and protein structure recovery to its native conformation, necessary to cease pathogenesis of neurodegenerative diseases. To substantiate our hypothesis, we conduct research in two separate projects, one traditional neurodegeneration project and the second, related to the impact of TH radiation on cancer treatment. At the initial stage, in close collaboration with physicists from Israel and Russia, we assemble a tunable device capable to emit terahertz radiation in its wide range. Once the device is operating, we will evaluate specific parameters necessary for dissolving of aggregated misfolded proteins, using amyloid beta as a proof of concept. Then we will evaluate impact of TH radiation on elimination of amyloid plaques in Alzheimer’s disease mice model, using 5XFAD mice. In case of successful elimination, we will conduct functional and behavioral assessment potential cognitive improvement. In cancer related project, we will evaluate viability of cancer cells under TH radiation in cell lines and xenograft tumors. In both cases, we will evaluate and optimize TH penetration depth and if necessary fiber optic technology will be used to locally deliver the radiation to the target tissues.

Success of this project will have not only fundamental and scientific, but a tremendous medically applicative value.

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Projects

1. Development and optimization of tunable Terahertz emitting device (in close collaboration with physicists, T001)

2. Investigation of optimal TH radiation ranges with maximal impact protein folding and elimination of misfolded proteins in neurodegenerative diseases using Alzheimer’s disease model (post-doctoral fellow, T002)

3. Investigation of optimal TH radiation ranges with maximal impact on cancer viability (post-doctoral fellow, T003)

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