Nanoformulated Mutant SurR9-C84A: a Possible Key for Alzheimer's and its Associated Inflammation

作者：Sriramoju Bhasker; Kanwar Rupinder K; Kanwar Jagat R^*

来源：Pharmaceutical Research, 2015, 32(8): 2787-2797.

DOI：10.1007/s11095-015-1664-8

• Alzheimer's disease
• inflammation
• neurodegeneration
• SurR9-C84A and beta-amyloid

Purpose Alzheimer's disease (AD) is one of the untreatable neurodegenerative diseases characterised by the pathologic amyloid plaque deposition and inflammation. The aim of this study is to evaluate the neuroprotective effects of nanoformulated SurR9-C84A, a survivin mutant belonging to the inhibitors of the apoptosis (IAP) protein family. The effect of SurR9-C84A was studied against the beta-amyloid toxicity and various inflammatory insults in the differentiated SK-N-SH neurons.
Method SurR9-C84A loaded poly(lactic-co-glycolic acid) nanoparticles were prepared following the modified double emulsion technique. The neuroprotective effect of SurR9-C84A was evaluated against the amyloid-beta (A beta) peptide fragment, N-methyl-D-aspartate (NMDA) toxicity and the inflammatory assaults. To mimic the in vivo situation, a co-culture of neurons and microglia was also studied to validate these results.
Results SurR9-C84A treatments showed improved neuronal health following A beta, and NMDA toxicity in addition to inflammatory insults induced in mono and co-cultures. The neuroprotective effect was evident with the reduced neuronal death, accelerated expression of neuronal integrity markers (neurofilaments, beta-tubulin III etc.,) and the neuroprotective ERK/MAPK signalling.
Conclusion The current results demonstrated that the SurR9-C84A nanoformulation was very effective in rescuing the neurons and holds a potential future application against AD.

• 出版日期2015-8
• 单位迪肯大学