TiO2 Nanowired Cerebrolysin reduces neuron-specific ubiquitin carboxyl-terminal esterase-L1 (UCHL1) in Alzheimer's Disease and brain pathology

Abstract

This innovation deals with involvement of neuron-specific ubiquitin carboxyl-terminal esterase-Ll (UCHL1) in Alzheimer's Disease (AD) induced brain pathology and neuroprotection by modulation of the enzyme with multimodal drug Cerebrolysin administered using TiO2-nanowired biotechnology in model experiments. AD like brain pathology was induced by intracerebroventricular (i.c.v.) administration of amyloid beta peptide (AβP 1-40, 250 ng/10 μl) daily for 4 weeks. This treatment resulted in significant elevation of UCHL1 in various brain regions associated with breakdown of the blood-brain barrier (BBB) and brain pathology. Administration of TiO2 nanowired Cerebrolysin (25 μl, NWCBL, i.c.v.) starting from 1 week after the onset of AβP infusion thwarted UCHL1 elevation and brain pathology. These observations are the first to demonstrate that nanodelivery of cerebrolysin is capable to attenuate AD pathology by modulating UCHL1 enzyme, not reported earlier.