Objective: To understand the role of mitochondrial function in improving the outcomes of Parkinson’s disease (PD) via pharmacologically activating PGC-1α by its synthetic activator ZLN005.
Background: Parkinson’s disease is a debilitating neurodegenerative disorder leading to severe motor abnormalities due to substantial loss of dopaminergic neurons. Dysfunctional mitochondrial homeostasis is an early hallmark of PD. Targeting mitochondrial abnormalities with therapeutic interventions may offer a promising strategy for halting the progression of Parkinson’s Disease.
Method: In Vitro experiments: Disease specific markers, mitochondrial biogenesis and control markers were evaluated by western blotting and immunofluorescence assays. Functional parameters like oxidative stress, mitochondrial density, and mitochondrial membrane potential were evaluated by flow cytometric analysis.
In Vivo experiments: Motor functions were assessed by rota rod, gait analysis, pole, and challenging beam test, followed by western blotting for the disease-specific and mitochondrial markers. Histological findings in the striatum and substantia nigra were performed.
Results: PGC-1α activator effectively counteracted the MPP+/MPTP induced toxicity improving motor function and preserving the expression of disease specific and mitochondrial proteins. Moreover, markers that transcriptionally activate PGC-1α were also upregulated and so are the markers involved in mitophagy. These findings were further corroborated by histological, and flow cytometry analysis highlighting its role in advancing mitochondrial health and mitigating oxidative stress.
Conclusion: PGC-1α activator, shows promise as a therapeutic agent in improving the outcomes of Parkinson’s disease by exerting neuroprotective effects through regulation of mitochondrial quality control.
To cite this abstract in AMA style:
J. Kaur, S. Naqvi. Pharmacological PGC-1α Activation Mitigates Dopaminergic Degeneration in Parkinson’s Disease Via Regulating Mitochondrial Homeostasis [abstract]. Mov Disord. 2025; 40 (suppl 1). https://www.mdsabstracts.org/abstract/pharmacological-pgc-1%ce%b1-activation-mitigates-dopaminergic-degeneration-in-parkinsons-disease-via-regulating-mitochondrial-homeostasis/. Accessed November 20, 2025.« Back to 2025 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/pharmacological-pgc-1%ce%b1-activation-mitigates-dopaminergic-degeneration-in-parkinsons-disease-via-regulating-mitochondrial-homeostasis/