CEREBROLYSIN REDUCES NEURON-SPECIFIC UCHL1 AND BRAIN PATHOLOGY IN ALZHEIMER’S DISEASE

Military personnel are vulnerable to traumatic brain injuries (TBI) as ne of the predisposing factors for Alzheimer’s disease (AD). TBI and AD both results in enhanced levels of plasma and cerebrospinal fluid (CSF) neuron-specific ubiquitin carboxyl-terminal esterase-L1 (UCHL1) and correlates well with the neurological symptoms of AD and brain pathologies. The UCHL1 is selectively expressed in neurons and an overload results in aggregation in AD brain. This would result in prevention of amyloid beta protein (AbP) degradation and/or clearance of AbP from the brain. Thus, whether reduction in levels of UCHL1 is reducing brain pathology in AD by the multimodal drug cerebrolysin that is known neuroprotective agent in AD. AD like brain pathology was induced by AbP (1-40) administration intraventricularly (i.c.v.) in the left lateral ventricle 250 ng/10 µl once daily for 4 weeks. After 30 days of the 1^stAbP infusion, the rats exhibited breakdown of the blood-brain barrier (BBB) extravasation of endogenous/exogenous protein tracers, brain edema formation and AbP deposits in several parts of the brain. Damages to neuronal, glial and/or axons are evident at this time. In these AD brains ELISA showed that the UCHL1 level increased by 250 to 300 % in the cortex, hippocampus and cerebellum in the areas showing AbP deposits. When TiO2 nanowired Cerebrolysin (25 µl, NWCBL) was infused into the left cerebral ventricles daily starting from 1 week after the onset of AbP infusion and terminated 1 week before the last infusion, a significant reduction in the UCHL1 levels in various parts of the brain was seen along with marked reduction in brain pathology. Neuronal loss, gliosis and AbP deposits were also significantly reduced in cerebrolysin treated AD group. This indicates that reduction in UCHL1 by TiO2-nanowired cerebrolysin plays key roles in reducing brain pathology in AD, not reported earlier.