Could glucagon like peptide-1 agonists be therapeutic targets in Parkinson’s Disease ?

Abstract

The therapeutic potential of glucagon-like peptide-1 (GLP-1) receptor agonists in Parkinson's Disease (PD) is an area of active investigation, with promising, albeit still preliminary, findings. While not a direct treatment for the underlying neurodegeneration, GLP-1 agonists may offer several beneficial effects relevant to PD pathology and symptoms: Some studies suggest GLP-1 agonists may exert neuroprotective effects by reducing oxidative stress, inflammation, and apoptosis (programmed cell death) in dopaminergic neurons. This is partly attributed to their ability to stimulate neurotrophic factors like brain-derived neurotrophic factor (BDNF). Improved Mitochondrial Function: Mitochondrial dysfunction plays a significant role in PD pathogenesis. GLP-1 agonists have shown to improve mitochondrial function and biogenesis, potentially mitigating the energy deficits seen in PD. Given the growing understanding of the gut-brain axis in PD, the impact of GLP-1 agonists on gut microbiota composition and function is of interest. These agonists may indirectly influence the gut environment, potentially reducing inflammation and improving gut barrier integrity, factors implicated in PD progression. Many individuals with PD experience metabolic complications, including weight loss, insulin resistance, and diabetes. GLP-1 agonists' well-established effects on glucose homeostasis, appetite regulation, and weight management could indirectly improve overall health and quality of life in PD patients. Some studies have reported improvements in motor symptoms in PD patients treated with GLP-1 agonists, although the mechanism behind this is not fully understood and requires further investigation. It could be related to their influence on neurotransmitter systems or improved overall health. However, it's crucial to acknowledge limitations: Current evidence is largely based on preclinical studies and small clinical trials. Larger, well-designed clinical trials are needed to definitively establish the efficacy and safety of GLP-1 agonists as a treatment for PD. The potential mechanisms of action still require further elucidation. Furthermore, the optimal dosage and duration of treatment remain to be determined. In summary, while the evidence is promising, GLP-1 receptor agonists are not yet established as a therapy for PD. Further research is needed to fully assess their therapeutic potential and determine their role within a comprehensive PD management strategy.