Research progress on gas signal molecular therapy for Parkinson's disease

The pathogenesis of Parkinson's disease (PD) remains unclear. Among the pathological manifestations is the progressive degeneration of the nigrostriatal dopaminergic pathway, leading to massive loss of neurons in the substantia nigra pars compacta and dopamine (DA) depletion. Therefore, the current drug treatment is primarily based on DA supplementation and delaying the progression of the disease. However, as patients' symptoms continue to worsen, the drug effect will gradually decrease or even disappear, thereby further aggravating clinical symptoms. Gas signaling molecules, such as hydrogen sulfide (H₂S), nitric oxide (NO), carbon monoxide (CO), and hydrogen (H₂), exhibit pleiotropic biological functions and play crucial roles in physiological and pathological effects. In common neurodegenerative diseases including Alzheimer's disease and PD, gas signal molecules can prevent or delay disease occurrence via the primary mechanisms of antioxidation, anti-inflammatory response, and antiapoptosis. This article reviews the therapeutic progress of gas signaling molecules in PD models and discusses the possibility of their clinical applications.