Does neurotrophic factor benefit to PD therapy via co-function with ubiquitin-proteasome system?

摘要

Parkinson's disease (PD) is a common progressive neurodegenerative disorder whose core symptoms are tremor, bradykinesia, rigidity, and postural instability. Currently available treatment of PD is mainly based on dopamine replacement strategy to provide relief of motor symptoms, but cannot halt or reverse the degenerative processes of disease. Considerable in vitro and in vivo studies have found that neurotrophic factor (NTF) has neuroprotective or even neurorestorative properties on dopaminergic (DA) system, promoting them become promising candidates for the treatment of PD. However, the precise mechanism of NTF's effect in PD remains to be elucidated. Though the etiopathogenesis of PD has remained elusive, recently, compelling evidence has converged to suggest that failure of the ubiquitin-proteasome system (UPS) to degrade unwanted proteins may underlie nigralstrital degeneration and Lewy body (LB) formation which occurs in PD. In support of this, proteasome inhibitor has been successfully induced a PD modal both in vivo and in vitro. Many NTFs have been proved to possess definitely a therapy effect in a PD animal modal. Whether NTF can co-function with UPS that accomplishes the aim to protect and reserve dopaminergic neurons' function from neurotoxicity injury induced by proteasome inhibitor? If this hypothesis could be confirmed, it will represent a valuable advancement in the study of PD. Moreover, investigation of the functional link between UPS and NTF should also provide useful information for understanding the pathogenesis of PD.