Oxytocin Nanogels Inhibit Innate Inflammatory Response for Early Intervention in Alzheimer's Disease.
Caihua YeMeng ChengLin MaTianzhu ZhangZuhao SunChunshui YuJunping WangYan DouPublished in: ACS applied materials & interfaces (2022)
Prevention of Alzheimer's disease (AD) is a global imperative, but reliable early interventions are currently lacking. Microglia-mediated chronic neuroinflammation is thought to occur in the early stage of AD and plays a critical role in AD pathogenesis. Here, oxytocin (OT)-loaded angiopep-2-modified chitosan nanogels (AOC NGs) were designed for early treatment of AD via inhibiting innate inflammatory response. Through the effective transcytosis of angiopep-2, AOC NGs were driven intravenously to cross the blood-brain barrier, enter the brain, and enrich in brain areas affected by AD. A large amount of OT was then released and specifically bound to the pathological upregulated OT receptor, thus effectively inhibiting microglial activation and reducing inflammatory cytokine levels through blocking the ERK/p38 MAPK and COX-2/iNOS NF-κB signaling pathways. Consecutive weekly intravenous administration of AOC NGs into 12-week-old young APP/PS1 mice, representing the early stage of AD, remarkably slowed the progression of Aβ deposition and neuronal apoptosis in the APP/PS1 mice as they aged and ultimately prevented cognitive impairment and delayed hippocampal atrophy. Together, the findings suggest that AOC NGs, which show good biosafety, can serve as a promising therapeutic candidate to combat neuroinflammation for early prevention of AD.
Keyphrases
- inflammatory response
- lps induced
- signaling pathway
- early stage
- lipopolysaccharide induced
- cognitive impairment
- cerebral ischemia
- immune response
- drug delivery
- oxidative stress
- toll like receptor
- traumatic brain injury
- randomized controlled trial
- pi k akt
- physical activity
- blood brain barrier
- cell proliferation
- epithelial mesenchymal transition
- neuropathic pain
- multiple sclerosis
- clinical trial
- high dose
- spinal cord injury
- resting state
- subarachnoid hemorrhage
- induced apoptosis
- low dose
- brain injury
- squamous cell carcinoma
- smoking cessation
- nitric oxide synthase
- replacement therapy
- middle aged
- wound healing
- functional connectivity