Journal
SCIENTIFIC REPORTS
Volume 7, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41598-017-15215-w
Keywords
-
Categories
Funding
- Instituto de Salud Carlos III (ISCIII) [PI14/01134, PI13/00364]
- European Regional Development Fund, (FEDER)
- Fundacio La Marato de TV3 [40/U/2014]
- Miguel Servet programme, ISCIII, Spain [CP12/03259]
- Spanish MINECO through the Severo Ochoa Centres of Excellence Programme [SEV-2013-0295]
Ask authors/readers for more resources
Cerebral beta-amyloidosis is a major feature of Alzheimer's disease (AD), characterized by the accumulation of beta-amyloid protein (A beta) 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 A beta, 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 A beta 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 A beta 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available