Glutathione S-transferase: A keystone in Parkinson's disease pathogenesis and therapy

Abstract

Parkinson's disease is a progressive neurodegenerative disorder that predominantly affects motor function due to the loss of dopaminergic neurons in the substantia nigra. It presents significant challenges, impacting millions worldwide with symptoms such as tremors, rigidity, bradykinesia, and postural instability, leading to decreased quality of life and increased morbidity. The pathogenesis of Parkinson's disease is multifaceted, involving complex interactions between genetic susceptibility, environmental factors, and aging, with oxidative stress playing a central role in neuronal degeneration. Glutathione S-Transferase enzymes are critical in the cellular defense mechanism against oxidative stress, catalysing the conjugation of the antioxidant glutathione to various toxic compounds, thereby facilitating their detoxification. Recent research underscores the importance of Glutathione S-Transferase in the pathophysiology of Parkinson's disease, revealing that genetic polymorphisms in Glutathione S-Transferase genes influence the risk and progression of the disease. These genetic variations can affect the enzymatic activity of Glutathione S-Transferase, thereby modulating an individual's capacity to detoxify reactive oxygen species and xenobiotics, which are implicated in Parkinson's disease neuropathological processes. Moreover, biochemical studies have elucidated the role of Glutathione S-Transferase in not only maintaining cellular redox balance but also in modulating various cellular signalling pathways, highlighting its neuroprotective potential. From a therapeutic perspective, targeting Glutathione S-Transferase pathways offers promising avenues for the development of novel treatments aimed at enhancing neuroprotection and mitigating disease progression. This review explores the evident and hypothesized roles of Glutathione S-Transferase in Parkinson's disease, providing a comprehensive overview of its importance and potential as a target for therapeutic intervention.