title: Nanoformulated Mutant SurR9-C84A: a Possible Key for Alzheimer's and its Associated Inflammation.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  The current results demonstrated that the SurR9-C84A nanoformulation was very effective in rescuing the neurons and holds a potential future application against AD.
authors.affiliation: 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.
authors.forename: Bhasker
authors.initials: B
authors.lastname: Sriramoju
authors.forename: Rupinder K
authors.initials: RK
authors.lastname: Kanwar
authors.forename: Jagat R
authors.initials: JR
authors.lastname: Kanwar
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000633:toxicity; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002626:Chemistry, Pharmaceutical; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy*; D051034:Inhibitor of Apoptosis Proteins / Q000627:therapeutic use*; D019344:Lactic Acid; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000633:toxicity; D017628:Microglia / Q000187:drug effects; D053758:Nanoparticles; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D000077022:Survivin
chemical_list: D016229:Amyloid beta-Peptides; D000893:Anti-Inflammatory Agents; C107489:BIRC5 protein, human; D016207:Cytokines; D051034:Inhibitor of Apoptosis Proteins; D008070:Lipopolysaccharides; D018696:Neuroprotective Agents; D000077022:Survivin; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid