| First Author | Fernández-de-Retana S | Year | 2017 |
| Journal | Sci Rep | Volume | 7 |
| Issue | 1 | Pages | 14637 |
| PubMed ID | 29116115 | Mgi Jnum | J:257366 |
| Mgi Id | MGI:6110537 | Doi | 10.1038/s41598-017-15215-w |
| Citation | Fernandez-de-Retana S, et al. (2017) Characterization of ApoJ-reconstituted high-density lipoprotein (rHDL) nanodisc for the potential treatment of cerebral beta-amyloidosis. Sci Rep 7(1):14637 |
| abstractText | Cerebral beta-amyloidosis is a major feature of Alzheimer''s disease (AD), characterized by the accumulation of beta-amyloid protein (Abeta) in the brain. Several studies have implicated lipid/lipoprotein metabolism in the regulation of beta-amyloidosis. In this regard, HDL (High Density Lipoprotein)-based therapies could ameliorate pathological features associated with AD. As apolipoprotein J (ApoJ) is a natural chaperone that interacts with Abeta, avoiding its aggregation and toxicity, in this study we propose to prepare reconstituted rHDL-rApoJ nanoparticles by assembling phospholipids with recombinant human ApoJ (rApoJ). Hence, rHDL particles were prepared using the cholate dialysis method and characterized by N-PAGE, dynamic light scattering, circular dichroism and electron transmission microscopy. The preparation of rHDL particles showed two-sized populations with discoidal shape. Functionally, rHDL-rApoJ maintained the ability to prevent the Abeta fibrillization and mediated a higher cholesterol efflux from cultured macrophages. Fluorescently-labelled rHDL-rApoJ nanoparticles were intravenously administrated in mice and their distribution over time was determined using an IVIS Xenogen(R) imager. It was confirmed that rHDL-rApoJ accumulated in the cranial region, especially in old transgenic mice presenting a high cerebral Abeta load. In conclusion, we have standardized a reproducible protocol to produce rHDL-rApoJ nanoparticles, which may be potentially considered as a therapeutic option for beta-amyloid-related pathologies. |
