Intranasal route in a transgenic model of Alzheimer: Nanomedicine Drug Therapy.

MARIA EUGENIA NAVAS GUIMARAES; MARIA BEATRIZ BISTUÉ MILLÓN; EDUARDO FERNÁNDEZ-MEGÍA; MARTIN A. BRUNO

Buenos Aires

Conferencia; Conference of Federation of Latin-American and Caribbean Societies for Neuroscience (FALAN)C; 2016

FALAN

A range of dietary and lifestyle factors have been linked to increasing or decreasing the risk of developing AD. However, the definitive causes of sporadic forms of AD are still unresolved, and this limits the developments of therapeutics strategies to treat the disease. In recent studies, the initiation and progression of AD has been linked to cholesterol metabolism, processes that can be modulated by cerebral expression of liver x receptors (LXRs). In this regard, enhanced expression of ApoE, through the activation of LXRs; facilitate the proteolytic clearance of amyloid beta from the brain. Recent in vivo studies using AD-like transgenic animal model revealed that LXRs agonists provoked inhibition of neuroinflammation, marked decrease cortical levels of amyloid beta and reversed contextual memory deficits. Unfortunately, these generation of LXRs agonists causes liver steatosis and hypertriglyceridemia, limiting its clinical application. The purpose of our research is aimed to test the effectiveness of a novel LXRs agonist, called DMHCA, in an AD-like transgenic mouse model. Due to the fact that DMHCA does not cross the blood-brain barrier, intranasal administered dendrimer-DMHCA-FITC complex are being tested to fully describe its penetration, biodistribution and specific effects in the target areas of the mouse brain. As an alternative therapeutics approach, dendrimer-DMHCA treatment should attenuates neuroinflammation, limit cortical oxidative stress damage and facilitate the proteolytic degradation of amyloid beta; characteristic of our mouse model of AD; without undesirable side effects. Such studies should render suitable preclinical proof of principle for further clinical application.