Tailoring Biomolecular Interactions of Hybrid Nanostructures for their Diagnostic and Therapeutic Applications in Neurodegenerative Diseases

Abstract

Alzheimer and Parkinson disease are common neurodegenerative disorders characterized by progressive structural and functional loss of the central nervous system. The foremost neuropathological events involve oxidative stress, mitochondrial dysfunction, inflammation and apoptosis. The disease-specific proteinopathies consists soluble aggregates including oligomers and protofibrils along with their phosphorylated variants deposited as plaque. The dynamic adsorption of these proteins on nanoparticle surface bestows with different physicochemical features and elicits the biological response. We show, in our approach molecular chemistry and optical characteristics of curcumin were used to elucidate the lanthanum carbonate nanospheres (REM100) and protein interactions via spontaneous binding of Aβ monomer and Aβ aggregates on Curcumin-REM100. The Protein concentration-dependent steady-state fluorescence enhancement of the curcumin and Langmuir protein adsorption model elucidates the maximum surface coverage and an apparent dissociation constant. Based on all experimental outcomes we demonstrated curcumin-REM100 as an efficient fluorescent probe able to delineate the monomer and the aggregate state of Amyloid-β with the Limit of detection (LOD) of 0.2 ±0.045 μM, the value is 30 times more sensitive than conventional Thioflavin-T (ThT) fluorescence emission intensity. The therapeutic approach uses the melatonin enriched polydopamine nanostructures for triggering robust neuroprotection against rotenone-induced neuroblastoma PD model. This causes reduction in cellular ROS level, re-establishing mitochondrial membrane potential, inhibiting caspase-dependent and independent apoptosis pathway and reducing alpha-synuclein phosphorylation at serine 129. The further in-vitro and organotypic mice brain slice culture-based therapeutic assessments have shown the superior neuroprotective potential of the developed nanoformulation. Considering the emerging interest in development of hybrid nanoformulation, our approaches elucidated diagnostic and therapeutic interventions in common neurodegenerative diseases.