Characterization of ApoJ-reconstituted high-density lipoprotein (rHDL) nanodisc for the potential treatment of cerebral beta-amyloidosis
Por:
Fernandez-de-Retana, S, Cano-Sarabia, M, Marazuela, P, Sanchez-Quesada, JL, Garcia-Leon, A, Montanola, A, Montaner, J, Maspoch, D, Hernandez-Guillamon, M
Publicada:
7 nov 2017
Resumen:
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.
Filiaciones:
Fernandez-de-Retana, S:
Univ Autonoma Barcelona, Vall dHebron Res Inst, Neurovasc Res Lab, Barcelona, Spain
Cano-Sarabia, M:
CSIC, Catalan Inst Nanosci & Nanotechnol ICN2, Campus UAB, Barcelona, Spain
Barcelona Inst Sci & Technol, Campus UAB, Barcelona, Spain
Marazuela, P:
Univ Autonoma Barcelona, Vall dHebron Res Inst, Neurovasc Res Lab, Barcelona, Spain
Sanchez-Quesada, JL:
Hosp St Pau IIB Sant Pau, Res Inst, Cardiovasc Biochem Grp, Barcelona, Spain
Garcia-Leon, A:
Hosp St Pau IIB Sant Pau, Res Inst, Cardiovasc Biochem Grp, Barcelona, Spain
Montanola, A:
Univ Autonoma Barcelona, Vall dHebron Res Inst, Neurovasc Res Lab, Barcelona, Spain
Montaner, J:
Univ Autonoma Barcelona, Vall dHebron Res Inst, Neurovasc Res Lab, Barcelona, Spain
Maspoch, D:
CSIC, Catalan Inst Nanosci & Nanotechnol ICN2, Campus UAB, Barcelona, Spain
ICREA, Barcelona 08100, Spain
Barcelona Inst Sci & Technol, Campus UAB, Barcelona, Spain
Hernandez-Guillamon, M:
Univ Autonoma Barcelona, Vall dHebron Res Inst, Neurovasc Res Lab, Barcelona, Spain
Gold, Green Published
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