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

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Abstract

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 β-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-β (Aβ) 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 Aβ, 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.

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Abbreviations

AD:

Alzheimer’s disease

Aβ:

Amyloid β fragment

ICC:

Immunocytochemistry

IGF:

Insulin like growth factor-1

LDH:

Lactate dehydrogenase

MBP:

Myelin basic protein

NF:

Neurofilament

NGF:

Nerve growth factor

NSE:

Neuron specific enolase

PLGA:

Poly (D,L-lactide-co-glycolide)

PMA:

Phorbol-12-myristate-13-acetate

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ACKNOWLEDGMENTS AND DISCLOSURES

The authors would like to thank the Australia–India Strategic Research Fund (AISRF, BF030016/42) and National Health and Medical Research Council (NHMRC, APP1050286) for financial support. This manuscript has not been published and is not under consideration for publication elsewhere and we have no conflicts of interest to disclose. No writing assistance was utilized in the production of this manuscript.

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Authors and Affiliations

  1. Nanomedicine Laboratory of Immunology and Molecular Biomedical Research (NLIMBR), School of Medicine (SoM), Molecular and Medical Research (MMR) Strategic Research Centre, Faculty of Health, Deakin University, Geelong Technology Precinct (GTP), Pigdons Road, Waurn Ponds, Geelong, Victoria, 3216, Australia

    Bhasker Sriramoju, Rupinder K. Kanwar & Jagat R. Kanwar

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  1. Bhasker Sriramoju
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  2. Rupinder K. Kanwar
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Correspondence to Jagat R. Kanwar.

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Sriramoju, B., Kanwar, R.K. & Kanwar, J.R. Nanoformulated Mutant SurR9-C84A: a Possible Key for Alzheimer’s and its Associated Inflammation. Pharm Res 32, 2787–2797 (2015). https://doi.org/10.1007/s11095-015-1664-8

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  • DOI: https://doi.org/10.1007/s11095-015-1664-8

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