title: Protective effects of octacosanol on 6-hydroxydopamine-induced Parkinsonism in rats via regulation of ProNGF and NGF signaling.
abstract: OBJECTIVE
  To investigate the protective effects of octacosanol in 6-hydroxydopamine-induced Parkinsonian rats and find whether octacosanol has effects on pro nerve growth factor (pro-NGF), NGF and the downstream effector proteins.
  
  
  METHODS
  Behavioral tests, enzymatic assay, tyrosine hydroxylase immunohistochemistry, TUNEL and Western blot were used to investigate the effects of octacosanol in this rat model of PD.
  
  
  RESULTS
  Oral administration of octacosanol (35-70 mg/kg, po for 14 d) significantly improved the behavioral impairments in rats induced by 6-OHDA and dose-dependently preserved the free radical scavenging capability of the striatum. Octacosanol treatment also effectively ameliorated morphological appearances of TH-positive neuronal cells in nigrostriatal systems and decreased the apoptotic cells induced by 6-OHDA in striatum. In addition, octacosanol strikingly blocked the 6-OHDA-induced increased expression of proNGF-p75NTR-sortilin death signaling complex and its downstream effector proteins. Meantime, octacosanol prevented the decreased levels of NGF, its receptors TrkA and p-Akt which together mediated the cell survival pathway.
  
  
  CONCLUSIONS
  The findings implicated that the anti-parkinsonism effects afforded by octacosanol might be mediated by its neuro-microenvironment improving potency through retrieving the ratios of proNGF:NGF and the respective receptors p75NTR:TrkA in vivo. Due to its excellent tolerability and non-toxicity, octacosanol may be a promising agent for PD treatment.
authors.affiliation: Department of Pharmacology, Institute of Basic Medical Sciences, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Yan-yong
authors.initials: YY
authors.lastname: Liu
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Nan
authors.initials: N
authors.lastname: Yang
authors.forename: Hai-bo
authors.initials: HB
authors.lastname: Zhu
authors.forename: Ping-ping
authors.initials: PP
authors.lastname: Zuo
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D015153:Blotting, Western; D004305:Dose-Response Relationship, Drug; D005233:Fatty Alcohols / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D008297:Male; D020932:Nerve Growth Factor / Q000187:drug effects / Q000378:metabolism; D009414:Nerve Growth Factors / Q000187:drug effects / Q000378:metabolism; D009419:Nerve Tissue Proteins; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000503:physiopathology; D011498:Protein Precursors / Q000187:drug effects / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020917:Receptor, trkA / Q000378:metabolism; D017978:Receptors, Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism
chemical_list: D000978:Antiparkinson Agents; D005233:Fatty Alcohols; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D011498:Protein Precursors; D017978:Receptors, Growth Factor; D017475:Receptors, Nerve Growth Factor; C514218:pro-nerve growth factor, rat; C068313:Ngfr protein, rat; C044309:1-octacosanol; D016627:Oxidopamine; D020932:Nerve Growth Factor; D020917:Receptor, trkA; D051057:Proto-Oncogene Proteins c-akt