Background: 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. Methods: 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. Results: 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. Conclusion: 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.

Keywords:
Phosphorylated tau, PI3K/Akt, Parkinson’s disease, GSK3β, Liposomes, Basic fibroblast growth factor
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