Blood-brain and blood-cerebrospinal fluid passage of BRICHOS domains from two molecular chaperones in mice [Protein Structure and Folding]

Targeting toxicity associated with amyloid-β (Aβ) misfolding and aggregation is a promising therapeutic strategy for preventing or managing Alzheimer's disease (AD). The BRICHOS domains from human prosurfactant protein C (proSP-C) and integral membrane protein 2B (Bri2) efficiently reduce neurotoxicity associated with Aβ42 fibril formation both in vitro and in vivo. In this study, we have evaluated the serum half-lives and permeability into the brain and the cerebrospinal fluid (CSF) of recombinant human (rh) proSP-C and Bri2 BRICHOS domains intravenously injected into wild type mice. We found that rh proSP-C BRICHOS has a longer blood serum half-life compared to rh Bri2 BRICHOS and passed into the CSF but not into the brain parenchyma. As judged by western blots, immunohistochemistry and ELISA assays, rh Bri2 BRICHOS passed into both CSF and brain. Intracellular immunostaining for rh Bri2 BRICHOS was observed in the choroid plexus epithelium as well as in the cerebral cortex. Our results indicate that intravenously administered rh proSP-C and Bri2 BRICHOS domains have different pharmacokinetic properties and blood-brain/blood-CSF permeabilities in mice. The finding that rh Bri2 BRICHOS can reach the brain parenchyma after peripheral administration may be harnessed in the search for new therapeutic strategies for managing AD.

from ! Human Diseases via Alexandros G.Sfakianakis on Inoreader http://bit.ly/2EYo6Y5