Objective: To clarity the effects and mechanism of poly-ADP-ribose polymerase 1(PARP1) in regulating mitochondrial fusion/fission in a rotenone-induced Parkinson’s disease (PD) model.
Background: Accumulating evidences suggest that PARP inhibitors can improve the parkinsonian motor and non-motor deficits in experimental cells and animals. The dysfunction of mitochondria and LRRK2 are key initiating factors in the pathogenesis of PD resulting in the death of dopaminergic neurons.
Method: Four common PARP1 inhibitors (ABT888 4uM, AG014699 5 uM, PJ34 3uM, Olaparib 5uM) were employed to intervene in rotenone-induced SH-SY5Y PD cell model. Neurotransmitters were detected by HPLC. The expression of PAR/PARP1, mitochondrial LRRK2, mitochondrial fusion/fission-related protein (Drp1, Mfn1, Mfn2, Opa1, Fis1) were detected by immunoprecipitation and immunofluorescence. The interaction between Drp1 and LRRK2 were detected by immunofluorescence, and mitochondrial morphology was detected by transmission electron microscopy.
Results: PARP1 inhibitor reversed mitochondrial fission and decreased mitochondrial membrane potential and protect the cytotoxic effects on rotenone-induced model. Significant morphological changes of mitochondria were observed in rotenone-induced cell which were reversed by PARP1 inhibitor AG014699. PAPR1 inhibitor intervention significantly attenuated the tyrosine-hydroxylase-positive neuron loss and contributed to mitochondrial fission via LRRK2.
Conclusion: Overall, our data showed that modulation of mitochondrial fusion/fission by PARP1 rescued the mitochondria dysfunction and resulted in neuroprotection form rotenone. In light of the safety and tolerance of PARP1 inhibitor administration, our results offering novel opportunities for the treatment of PD based on PARP1 inhibition and mitochondrial homeostasis.
To cite this abstract in AMA style:
L. Bu, Y. Lu, Y. Liang, Y. Chen, S. Peng. Poly-ADP-ribose polymerase 1 modulates mitochondrial fission via LRRK2 in a rotenone-induced Parkinson’s disease model [abstract]. Mov Disord. 2020; 35 (suppl 1). https://www.mdsabstracts.org/abstract/poly-adp-ribose-polymerase-1-modulates-mitochondrial-fission-via-lrrk2-in-a-rotenone-induced-parkinsons-disease-model/. Accessed July 12, 2025.« Back to MDS Virtual Congress 2020
MDS Abstracts - https://www.mdsabstracts.org/abstract/poly-adp-ribose-polymerase-1-modulates-mitochondrial-fission-via-lrrk2-in-a-rotenone-induced-parkinsons-disease-model/