Investigation of zinc dyshomeostasis associated with aging and dementia-related disorders using novel nanodiamond-based markers

Project Member(s): Shimoni, O.

Funding or Partner Organisation: National Health & Medical Research Council (NHMRC DEMENTIA RESEARCH DEVELOPMENT FELLOWSHIP)

Start year: 2016

Summary: Zinc ions (Zn2+) are the second most abundant transition metal ions in the brain after iron, and play a critical role in the control of physiological brain functions. It is well-acceptable that zinc is a key regulator linked to learning and memory functioning, but the zinc involvement in the memory disruption in dementia-linked diseases, such as Alzheimer's or Parkinson¿s diseases is not clear. To date, to elucidate and measure Zn2+ concentration in brain tissues, researchers has exploited several commercially available fluorescent probes, including Newport Green DCF¿, FluoZin-1¿, Fluozin-3¿. However, due to some well-acknowledged limitations of these probes, such as photobleaching, lack of site of specificity, compartmentalization in cellular vesicles and fast clearance from the cells, their reliability is questionable. Therefore, I propose to assemble novel Zn2+ sensors based on multi-fluorescent diamond nanoparticles that will be specifically targeted to the glutamatergic receptors in synapse. Such a highly specific sensor will provide explicit answers on establishing the physiological role of Zn2+ at different age stages, measuring change of zinc ions concentration precisely in the synaptic cleft, and/or evaluating zinc role in dementia-associated diseases. By understanding how Zn changes at the synapse across age and in disease, we might then be better able to understand mechanisms and then look towards therapeutic treatments.

Publications:

Georgevsky, D, Retsas, S, Raoufi, N, Shimoni, O & Golzan, SM 2019, 'A longitudinal assessment of retinal function and structure in the APP/PS1 transgenic mouse model of Alzheimer’s disease', Translational Neurodegeneration, vol. 8, no. 1, p. 30.
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Bray, K, Cheung, L, Hossain, KR, Aharonovich, I, Valenzuela, SM & Shimoni, O 2018, 'Versatile multicolor nanodiamond probes for intracellular imaging and targeted labeling', Journal of Materials Chemistry B, vol. 6, no. 19, pp. 3078-3084.
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Chen, Y, Duong, HTT, Wen, S, Mi, C, Zhou, Y, Shimoni, O, Valenzuela, SM & Jin, D 2018, 'Exonuclease III-Assisted Upconversion Resonance Energy Transfer in a Wash-Free Suspension DNA Assay', Analytical Chemistry, vol. 90, no. 1, pp. 663-668.
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Duong, HTT, Chen, Y, Tawfik, SA, Wen, S, Parviz, M, Shimoni, O & Jin, D 2018, 'Systematic investigation of functional ligands for colloidal stable upconversion nanoparticles', RSC Advances, vol. 8, no. 9, pp. 4842-4849.
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Kaur, A, Shimoni, O & Wallach, M 2018, 'Novel screening test for celiac disease using peptide functionalised gold nanoparticles', World Journal of Gastroenterology, vol. 24, no. 47, pp. 5379-5390.
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Sun, Y, Zhang, W, Wang, B, Xu, X, Chou, J, Shimoni, O, Ung, AT & Jin, D 2018, 'A supramolecular self-assembly strategy for upconversion nanoparticle bioconjugation', Chemical Communications, vol. 54, no. 31, pp. 3851-3854.
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Wang, F, Wen, S, He, H, Wang, B, Zhou, Z, Shimoni, O & Jin, D 2018, 'Microscopic inspection and tracking of single upconversion nanoparticles in living cells', Light: Science & Applications, vol. 7, no. 4, pp. 18007-18007.
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Wu, Y, Li, S, Liu, J, Liu, X, Ruan, W, Lu, J, Liu, Y, Lawson, T, Shimoni, O, Lovejoy, DB, Walker, AK, Cong, Y & Shi, B 2018, 'Stilbenes from Veratrum maackii Regel Protect against Ethanol-Induced DNA Damage in Mouse Cerebellum and Cerebral Cortex', ACS Chemical Neuroscience, vol. 9, no. 7, pp. 1616-1624.
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Kaur, A, Shimoni, O & Wallach, M 2017, 'Celiac disease: from etiological factors to evolving diagnostic approaches', Journal of Gastroenterology, vol. 52, no. 9, pp. 1001-1012.
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Bray, K, Cheung, L, Aharonovich, I, Valenzuela, SM & Shimoni, O 2017, 'Versatile Multicolor Nanodiamond Probes for Intracellular Imaging and Targeted Labeling', Cold Spring Harbor Laboratory.
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Shimoni, O, Shi, B, Adlard, PA & Bush, AI 2016, 'Delivery of Fluorescent Nanoparticles to the Brain', Journal of Molecular Neuroscience, vol. 60, no. 3, pp. 405-409.
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Keywords: dementia, zinc concentration, diamond nanoparticles

FOR Codes: Nanobiotechnology, Medical Biotechnology Diagnostics (incl. Biosensors), Neurology and Neuromuscular Diseases, Expanding Knowledge in Technology, Expanding Knowledge in the Medical and Health Sciences, EXPANDING KNOWLEDGE

Acknowledgement of Country

UTS acknowledges the Gadigal people of the Eora Nation, the Boorooberongal people of the Dharug Nation, the Bidiagal people and the Gamaygal people, upon whose ancestral lands our university stands. We would also like to pay respect to the Elders both past and present, acknowledging them as the traditional custodians of knowledge for these lands.