title: Acteoside Binds to Caspase-3 and Exerts Neuroprotection in the Rotenone Rat Model of Parkinson's Disease.
abstract: Parkinson's disease (PD) is characterized by the progressive degeneration of the dopaminergic neurons in the substantia nigra (SN) region. Acteoside has displayed multiple biological functions. Its potential role against PD and the underlying signaling mechanisms are largely unknown. Here, we showed that oral administration of acteoside significantly attenuated parkinsonism symptoms in rotenone-induced PD rats. Further, acteoside inhibited rotenone-induced α-synuclein, caspase-3 upregulation and microtubule-associated protein 2 (MAP2) downregulation in PD rats. The molecular docking and molecular dynamics (MD) simulation results indicated that acteoside may directly bind to and inhibit caspase-3. Acteoside formed hydrogen bonds with at least six residues of caspase-3: ThrA177, SerA178, GlyA238, SerB339, ArgB341 and TrpB348. In addition, a pi-pi interaction was formed between acteoside and caspase-3's HisA237, which might further stabilize the complex. MD simulation results demonstrated that the binding affinity of the caspase-3-acteoside complex was higher than that of caspase-3 and its native ligand inhibitor. Together, we show that acteoside binds to caspase-3 and exerts neuroprotection in the rotenone rat model of PD.
authors.affiliation: Department of Neurology, Shanghai Sixth People's Hospital affiliated to Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Jiawen
authors.initials: J
authors.lastname: Yuan
authors.affiliation: Department of Neurology, Shanghai Sixth People's Hospital affiliated to Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Jinpeng
authors.initials: J
authors.lastname: Ren
authors.affiliation: State Key Laboratory of Precision Spectroscopy and Department of Physics, East China Normal University, Shanghai, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Precision Spectroscopy and Department of Physics, East China Normal University, Shanghai, China.|NYU-ECNU Center for Computational Chemistry at NYU Shanghai, Shanghai, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: He
authors.affiliation: Department of Neurology, Shanghai Sixth People's Hospital affiliated to Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Yuwu
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000818:Animals; D053148:Caspase 3 / Q000378:metabolism*; D004195:Disease Models, Animal; D005960:Glucosides / Q000378:metabolism*; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D010300:Parkinson Disease / Q000517:prevention & control*; D010636:Phenols / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D012402:Rotenone / Q000009:adverse effects*; D051844:alpha-Synuclein / Q000378:metabolism; D059808:Polyphenols
chemical_list: D053148:Caspase 3; D005960:Glucosides; D008869:Microtubule-Associated Proteins; D010636:Phenols; D012402:Rotenone; D051844:alpha-Synuclein; C489787:MAP2 protein, rat; C058956:acteoside; D059808:Polyphenols