Roskamp Institute Articles Better Science. Real Discovery.

August 21, 2012

Stimulation of the retinoid X receptor facilitates beta-amyloid clearance across the blood-brain barrier.

Filed under: Uncategorized — Gogce Crynen @ 2:10 pm

July 30, 2012

Dr. Bachmeier and Dr. Paris recently published an article in Journal of Molecular Neuroscience titled “Stimulation of the retinoid X receptor facilitates beta-amyloid clearance across the blood-brain barrier”. This report identified a role for RXR stimulation in the clearance of Aβ across the BBB and examined the contribution of apoE to this process.

Abstract
Alzheimer’s disease (AD) is a neurodegenerative process characterized, in part, by the accumulation of beta-amyloid proteins (Aβ) in the brain. Evidence now suggests the excessive Aβ accumulation is the result of impaired clearance from the brain. Recent studies have indicated that retinoid X receptor (RXR) activation stimulates the metabolic clearance of Aβ and rapidly reverses Aβ-induced behavioral deficits, doing so in an apoE-dependent manner. Previously we reported that soluble apoE (i.e., not bound to Aβ) facilitated Aβ transit across the BBB. As Aβ clearance from the brain involves both metabolic and BBB-mediated processes, the current studies investigated the impact of RXR stimulation on Aβ clearance across the BBB. Treatment with RXR agonists increased Aβ clearance across the BBB both in vitro and in vivo. Moreover, this processes appeared to involve apoE as RXR agonism did not stimulate Aβ BBB clearance when apoE was absent. Thus, RXR activation could mitigate Aβ brain burden by promoting both the metabolic and BBB clearance of Aβ, offering a novel approach to the treatment of AD.

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