Effective Targeting of Aβ to Macrophages by Sonochemically Prepared Surface-Modified Protein Microspheres

Imbalanced homeostasis and oligomerization of the amyloid-β (Aβ) peptide in the brain are hallmarks of Alzheimer’s disease (AD). Microglia and macrophages play a critical role in the etiology of AD either by clearing Aβ from the brain or inducing inflammation. Recent evidence suggests that clearance...

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Bibliographic Details
Published in:Biomacromolecules 2013-01, Vol.14 (1), p.110-116
Main Authors: Richman, Michal, Perelman, Alex, Gertler, Asaf, Rahimipour, Shai
Format: Article
Language:English
Subjects:
Amyloid beta-Peptides - administration & dosage
Amyloid beta-Peptides - metabolism
Animals
Applied sciences
Biological and medical sciences
Cattle
Cell Line
Cells, Cultured
Drug Delivery Systems - methods
Exact sciences and technology
Humans
Macrophages - drug effects
Macrophages - metabolism
Medical sciences
Mice
Microglia - chemistry
Microglia - metabolism
Microspheres
Neuropharmacology
Organic polymers
Phagocytosis - physiology
Pharmacology. Drug treatments
Physicochemistry of polymers
Properties and characterization
Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer
Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease)
Psychology. Psychoanalysis. Psychiatry
Psychopharmacology
Serum Albumin, Bovine - chemistry
Serum Albumin, Bovine - metabolism
Special properties (catalyst, reagent or carrier)
Surface Properties
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Summary:Imbalanced homeostasis and oligomerization of the amyloid-β (Aβ) peptide in the brain are hallmarks of Alzheimer’s disease (AD). Microglia and macrophages play a critical role in the etiology of AD either by clearing Aβ from the brain or inducing inflammation. Recent evidence suggests that clearance of Aβ by microglia/macrophages via the phagocytic pathway is defective in AD, which can contribute to the accumulation of Aβ in the brain. We have recently demonstrated that protein microspheres modified at their surface with multiple copies of an Aβ-recognition motif can strongly bind Aβ, inhibit its aggregation, and directly reduce its toxicity by sequestering it from the medium. Here, we describe how microsphere-bound Aβ can stimulate microglial cells and be phagocytosed through a mechanism that is distinct from that of Aβ removal and, thus, contribute to the clearance of Aβ, even by defective microglial cells. The phagocytosis was most effective, with microspheres having a diameter of
ISSN:1525-7797
1526-4602
DOI:10.1021/bm301401b