Hybrid nanostructures mediated biosensing and epigenetically controlled neurotherapeutic applications in neurodegenerative diseases

Abstract

The present thesis elaborates the evolution of bioinspired hybrid nanostructures, their newlinetherapeutic potential and underlying neuroprotective mechanisms for the two most common and newlineprevalent neurodegenerative diseases worldwide namely Alzheimer s disease (AD) and newlineParkinson s disease (PD). Predominantly, the role of two neurohormones, dopamine and newlinemelatonin, has been investigated in the regulation of these neurodegenerative diseases; newlinehowever, the evolution of nanosized hybrid structures from these precursors under newlinephysiologically stressed environment was the new development emphasized in the thesis. The newlinepresent newlinenanostructures newlineshowed newlinebrain newlinetissue newlineaccumulation, newlinesustainable newlinerelease newlineof newlineneuroprotective melatonin, and prevents PD progression. The synergistic neuroprotection re- newlineestablishes the mitochondrial membrane potential, suppresses cellular reactive oxygen species newline(ROS) generation, inhibits activation of both caspase-dependent and independent apoptotic newlinepathways and confer a strong anti-inflammatory effect. It suppresses and#945;-synuclein newlinephosphorylation at Serine 129 pand#945;-SYN (S129) with reduced pathological processing, and newlinecellular accumulations investigated in ex-vivo organotypic brain slice culture and in-vivo newlineexperimental PD models. The epigenetic polycomb repressor complex 1 (PRC1) subunit BMI- newline1, which plays a crucial role in the repression of key regulatory genes in neurogenic tissues newlinelinked as a critical negative regulator of pand#945;-SYN (S129) and underlying regulatory mechanism newlineof pathogenic processing in different PD models. newline