Synergic treatment of Alzheimer’s disease with brain targeted nanoparticles incorporating NgR-siRNA and brain derived neurotrophic factor

Abstract

The decrease and functional failure of the central cholinergic neurons caused by degeneration and necrosis, not only directly led to a series of clinical symptoms of Alzheimer’s disease (AD), but also seriously affected the efficacy of cholinesterase inhibitors. At present, the clinical treatment of AD has extremely limited effect. In this work, a novel nanoparticle incorporating Nogo Receptor-siRNA (NgR-siRNA) and brain derived neurotrophic factor (BDNF) was designed and synthesized to realize the synergic treatment of AD with high efficiency. After brain-targeted modification, the nanoparticles overcome the blood-brain barrier were delivered into the basal forebrain and temporal hippocampus of the AD model by tail vein and brain-directed injection to achieve the effective promotion of the regeneration and repair of cholinergic neurons. The experimental results showed that the proposed nanoparticles could efficiently eliminate the limitations of currently AD treatment methods, enabling it a promising and reliable nanoplatform for AD treatment.

Keywords

• Alzheimer’s disease
• Brain derived neurotrophic factor
• Nogo repector
• siRNA
• Nanoparticles