title: Human Basic Fibroblast Growth Factor Inhibits Tau Phosphorylation via the PI3K/Akt-GSK3β Signaling Pathway in a 6-Hydroxydopamine-Induced Model of Parkinson's Disease.
abstract: Basic fibroblast growth factor (bFGF) has been increasingly investigated due to its neuroprotection in neurodegenerative disorders. Because there are still no cures for any of these disorders, it is crucial to identify new therapeutic targets and screen potential drugs. The increased phosphorylation of tau at Ser396 leads to intracellular tau accumulation, which forms neurofibrillary tangles in Parkinson's disease (PD). In this study, neuroprotection by bFGF was observed, and the mechanisms related to its regulation of phosphorylated tau were investigated.
  
  
  
  bFGF-loaded liposome carriers were intranasally administered to rats. The neuroprotective effects of bFGF were assessed in a PD model induced by 6-hydroxydopamine (6-OHDA) in vivo and in vitro. The phosphorylation of tau was measured, and the PI3K/Akt-GSK3β signaling pathway was investigated.
  
  
  
  Our study demonstrated that liposomes markedly assisted in the delivery of bFGF to the striatum and substantia nigra of rats and enhanced the neuroprotective effects of bFGF on dopaminergic neurons. bFGF treatment significantly ameliorated the behavioral deficits induced by 6-OHDA, rescued the loss of tyrosine hydroxylase-positive neurons and increased the number of Nissl bodies. bFGF reduced the phosphorylation of tau and GSK3β and increased the phosphorylation of PI3K/Akt.
  
  
  
  Liposomes markedly assisted in the delivery of bFGF to the brain and enhanced the neuroprotective effects of bFGF by inhibiting the phosphorylation of tau. bFGF down-regulated the phosphorylation of tau by increasing the phosphorylation of GSK3β via the PI3K/Akt signaling pathway. These findings provide a new vision of bFGF as a potential therapy for PD.
authors.affiliation: Institute of Biomedicine and National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou, China.
authors.forename: Peng-Hui
authors.initials: PH
authors.lastname: Yang
authors.forename: Jian-Xiu
authors.initials: JX
authors.lastname: Zhu
authors.forename: Ya-Dong
authors.initials: YD
authors.lastname: Huang
authors.forename: Xian-Ying
authors.initials: XY
authors.lastname: Zhang
authors.forename: Peng
authors.initials: P
authors.lastname: Lei
authors.forename: Ashley I
authors.initials: AI
authors.lastname: Bush
authors.forename: Qi
authors.initials: Q
authors.lastname: Xiang
authors.forename: Zhi-Jian
authors.initials: ZJ
authors.lastname: Su
authors.forename: Qi-Hao
authors.initials: QH
authors.lastname: Zhang
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D045744:Cell Line, Tumor; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism; D004337:Drug Carriers / Q000008:administration & dosage / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage* / Q000627:therapeutic use; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism; D006801:Humans; D008081:Liposomes / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D016627:Oxidopamine; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism*; D020734:Parkinsonian Disorders / Q000188:drug therapy / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D004337:Drug Carriers; D008081:Liposomes; C054369:MAPT protein, human; D018696:Neuroprotective Agents; D016875:tau Proteins; D016222:Fibroblast Growth Factor 2; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D019869:Phosphatidylinositol 3-Kinases; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt