Abstract
2014 Biologically inspired nanostructures dedicated to Alzheimer’s disease treatment Evaluation of: Song Q, Huang M, Yao L et al. Lipoprotein-based nanoparticles rescue the memory loss of mice with Alzheimer’s disease by accelerating the clearance of amyloid-beta. ACS Nano 8(3), 2345–2359 (2014). Alzheimer disease (AD) is the most widespread form of dementia worldwide. This pathology is mainly related to amyloid-β (Aβ) peptide aggregation and accumulation in the brain leading to neuronal death. Aβ clearance appeared as a promising approach for efficient AD therapy. Clearance techniques involving anti-Aβ antibodies have been successfully demonstrated but are still limited by autoimmunity adverse effects. Nano particles were also developed to capture Aβ and prevent their aggregation; nevertheless, these studies were only demonstrated at molecular level. In this paper, bioinspired nanoparticles were synthesized in order to improve Aβ capture and clearance in clinically relevant biological systems. Indeed, ApoE3rHDLs are natural nanoparticles (nanodisc structures of 28 nm) offering high affinity with Aβ and able to cross the blood–brain barrier. The synthesized biomimetic ApoE3rHDL provides many advantages such as smaller size, higher blood–brain barrier penetration and higher Aβ affinity compared with previous reported nanostructures involving apolipoprotein (ApoE). Aβ capture efficiency using ApoE3rHDL under physiological conditions (cerebrospinal fluid and plasma matrices) was demonstrated. The authors also evidenced the influence of ApoE3rHDL on Aβ degradation efficiency. Indeed microglia and astrocyte cells are known to be involved in Aβ degradation for brain clearance, thus it was demonstrated that 3 h after ApoE3rHDL injection, Aβ cellular uptake, lysosomal transport and intracellular degradation were significantly improved. Finally, the efficiency of ApoE3rHDL for in vivo clearance was demonstrated by injecting them in SAMP8. A decrease in Aβ deposition in the brain as well as an increase in spatial and learning memory compared with nontreated mice was observed. In summary, this paper highlights the potential of ApoE3rHDL to be used as an efficient biomimetic nanomedicine for AD therapy.
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