Session Information
Date: Wednesday, June 22, 2016
Session Title: Parkinson's disease: Neuroimaging and neurophysiology
Session Time: 12:00pm-1:30pm
Location: Exhibit Hall located in Hall B, Level 2
Objective: To investigate the role of lysosomal protease cathepsin L in the activation of microglia and the injury of dopaminergic neurons, and further to interpret the function of cathepsin L in the pathogenesis of Parkinson’s disease (PD).
Background: Inflammation induced by microglia plays an important role in the pathogenesis of PD. Lysosomal protease cathepsin L belongs to a member of the cysteine protease family and recently it was showed playing a role in the activation of macrophage and microglia. Our research focused on its function and underlying mechanism in the process of activation in microglia, thereby tried to find a new target to extenuate the excessive activation of microglia.
Methods: We used real-time PCR methods to clarify the difference of cathepsin L expression level in the peripheral blood mononuclear cells( PBMC) between 60 PD patients and 50 healthy control. Cathepsin L protein expression in BV-2 cells upon LPS stimulation was observed. Expression of iNOS, COX-2, TNF-α and IL-6 after inhibition of cathepsin L were studied. Inhibition of cathepsin L on LPS-induced p38, JNK, ERK, NF-κB and caspase-8 activation were also investigated.
Results: 1.The expression of cathepsin L mRNA was notably higher in PD patients than healthy individuals (P<0.05). 2. Cathepsin L protein expression was obviously up-regulated upon LPS stimulation in BV2 cells. 3. Inhibition of cathepsin L could significantly reduce the elevation of iNOS, COX-2, TNF-α and IL-6 expression induced by LPS stimulation. 4. Blocking cathepsin L could extenuate dopaminergic cell death exposed to the conditioned medium collected from LPS stimulated BV-2 cells. 5. Inhibition of cathepsin L could alleviate the activation of NF-κB and caspase-8 caused by LPS stimulation, and yet, had no effect on LPS-induced MAPK pathway.
Conclusions: Cathepsin L is involved in the neuroinflammation mediated by microglia depending on NF-κB and caspase-8 pathway, blocking cathepsin L can be a potential therapeutic approach to control the excessive activation of microglia.
To cite this abstract in AMA style:
S. Xu, X. Yang, H. Zhang, Y. Qian, Q. Xiao. The role of cathepsin L involved in the activation of microglia and Parkinson’s disease [abstract]. Mov Disord. 2016; 31 (suppl 2). https://www.mdsabstracts.org/abstract/the-role-of-cathepsin-l-involved-in-the-activation-of-microglia-and-parkinsons-disease/. Accessed September 25, 2023.« Back to 2016 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/the-role-of-cathepsin-l-involved-in-the-activation-of-microglia-and-parkinsons-disease/