title: Hypoestoxide reduces neuroinflammation and α-synuclein accumulation in a mouse model of Parkinson's disease.
abstract: BACKGROUND
  Deposition of α-synuclein and neuroinflammation are key pathological features of Parkinson's disease (PD). There is no cure for the disease; however, targeting the pathological features might be available to modulate the disease onset and progression. Hypoestoxide (HE) has been demonstrated as a NF-κB modulator, thereby acting as a potential anti-inflammatory and anti-cancer drug.
  
  
  METHODS
  In order to assess the effect of HE in a mouse model of PD, mThy1-α-syn transgenic mice received intraperitoneal (IP) injections of either vehicle or HE (5 mg/kg) daily for 4 weeks.
  
  
  RESULTS
  Treatment of HE decreased microgliosis, astrogliosis, and pro-inflammatory cytokine gene expression in α-syn transgenic mice. HE administration also prevented the loss of dopaminergic neurons and ameliorated motor behavioral deficits in the α-syn transgenic mice, and α-synuclein pathology was significantly reduced by treatment of HE. In addition, increased levels of nuclear phosphorylated NF-κB in the frontal cortex of α-syn transgenic mice were significantly reduced by HE administration.
  
  
  CONCLUSIONS
  These results support the therapeutic potential of HE for PD and other α-synuclein-related diseases.
authors.affiliation: Department of Neuroscience, University of California, San Diego, La Jolla, CA, 92093, USA. ckim@ucsd.edu.
authors.forename: Changyoun
authors.initials: C
authors.lastname: Kim
authors.affiliation: Immune Modulation, Inc., P.O. Box 998, Bloomington, CA, 92316-0998, USA. ojoamaize@aol.com.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Ojo-Amaize
authors.affiliation: Department of Neuroscience, University of California, San Diego, La Jolla, CA, 92093, USA. b1spencer@ucsd.edu.
authors.forename: Brian
authors.initials: B
authors.lastname: Spencer
authors.affiliation: Department of Neuroscience, University of California, San Diego, La Jolla, CA, 92093, USA. erockenstein@ucsd.edu.
authors.forename: Edward
authors.initials: E
authors.lastname: Rockenstein
authors.affiliation: Department of Neuroscience, University of California, San Diego, La Jolla, CA, 92093, USA. mmante@yahoo.com.
authors.forename: Michael
authors.initials: M
authors.lastname: Mante
authors.affiliation: Department of Neuroscience, University of California, San Diego, La Jolla, CA, 92093, USA. pdesplat@ucsd.edu.
authors.forename: Paula
authors.initials: P
authors.lastname: Desplats
authors.affiliation: Moores Cancer Center, University of California, San Diego, 2880 Torrey Pines Scenic Drive, La Jolla, CA, 92037, USA. wwrasidlo@ucsd.edu.
authors.forename: Wolf
authors.initials: W
authors.lastname: Wrasidlo
authors.affiliation: Department of Neuroscience, University of California, San Diego, La Jolla, CA, 92093, USA. asadame@ucsd.edu.
authors.forename: Anthony
authors.initials: A
authors.lastname: Adame
authors.affiliation: Immune Modulation, Inc., P.O. Box 998, Bloomington, CA, 92316-0998, USA. nchekwube@msn.com.
authors.forename: Emeka
authors.initials: E
authors.lastname: Nchekwube
authors.affiliation: Immune Modulation, Inc., P.O. Box 998, Bloomington, CA, 92316-0998, USA. oyem4yu@aol.com.
authors.forename: Olusola
authors.initials: O
authors.lastname: Oyemade
authors.affiliation: Immune Modulation, Inc., P.O. Box 998, Bloomington, CA, 92316-0998, USA. jokogun@yahoo.com.
authors.forename: Joseph
authors.initials: J
authors.lastname: Okogun
authors.affiliation: Moores Cancer Center, University of California, San Diego, 2880 Torrey Pines Scenic Drive, La Jolla, CA, 92037, USA. michan@ucsd.edu.
authors.forename: Michael
authors.initials: M
authors.lastname: Chan
authors.affiliation: Moores Cancer Center, University of California, San Diego, 2880 Torrey Pines Scenic Drive, La Jolla, CA, 92037, USA. hcottam@ucsd.edu.|Immune Modulation, Inc., P.O. Box 998, Bloomington, CA, 92316-0998, USA. hcottam@ucsd.edu.
authors.forename: Howard
authors.initials: H
authors.lastname: Cottam
authors.affiliation: Department of Neuroscience, University of California, San Diego, La Jolla, CA, 92093, USA. emasliah@ucsd.edu.|Pathology, School of Medicine, University of California, San Diego, La Jolla, CA, 92093, USA. emasliah@ucsd.edu.
authors.forename: Eliezer
authors.initials: E
authors.lastname: Masliah
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004224:Diterpenes / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D019579:Neocortex / Q000187:drug effects / Q000378:metabolism; D010300:Parkinson Disease / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D051844:alpha-Synuclein / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*
chemical_list: D004224:Diterpenes; D016328:NF-kappa B; D051844:alpha-Synuclein; C432343:hypoestoxide