Targeting senescent astrocytes/microglia for therapeutic intervention in PD
This study will allow us to understand the senescence aspects of neuropathology of PD, which may reveal potentially new therapeutic targets using senolytics for preventing neurodegeneration including PD. Currently we are testing senolytics in the PFF-injected PD mice and further developing a nanoparticle for a potential therapeutic application with a senolytic and ROS scavengers to target senescent and/or reactive damaged astrocytes (or microglia) in PD models.
Oxidative stress increases the levels of deSUMOylation in PD pathology
This approach will help us determine if stimulating SENP1 is related to induce the PD pathology in human and mouse brains and blocking SUMO1 removal by SENP1 inhibition can be a novel therapeutic target in PD pathology. Therefore, this approach will help identify how deSUMOylation could be targeted for potentially preventing or slowing pathological progress.
Assessing regulatory roles of SUMOylation in DAT, alpha-synuclein, & LRRK2
We found that the overexpression of Ubc9 protects rat dopaminergic N27 cells against MPP+ induced oxidative stress and PFF injection, via reduced ROS generation and protein aggregation (Verma et al., eNeuro, 2020). Therefore, SUMOylation of α-synuclein can be a potential therapeutic target for Parkinson’s disease. Currently we focus on assessing the role of SUMOylation on LRRK2 and the mechanisms of aberrant protein degradation by SUMOylation on α-synuclein
Developing neuroprotective compounds as potential PD therapeutics
The overall goal is to develop clinically safe, orally available anti-Parkinsonian drug candidates intended to significantly slow down or even reverse the disease pathology via the neuroprotective properties, in addition to relieving PD symptoms.
Developing a combination therapy & identifying a Biomarker in PD.
The use of low dose of lithium in combination with other potential or pre-existing therapeutic compounds may be a promising approach for alleviating symptoms as well as providing neuroprotective effects to halt the disease progression and other neurodegenerative diseases. In addition, currently we are assessing numerous saliva samples from human PD patients, in comparison with age- and gender-matched healthy control samples, for identifying a potential biomarker to detect or diagnose early stage