Liraglutide → Parkinsons Disease

Original Indication

Type 2 Diabetes Mellitus, Chronic Weight Management

Proposed New Indication

Repurposing Liraglutide for neuroprotection in Parkinson's Disease by restoring the ER-Mitochondrial axis, enhancing mitochondrial function, improving cellular bioenergetics, and promoting macroautophagy. This addresses chronic ER stress and mitochondrial dysfunction, key pathological contributors to dopaminergic degeneration in PD.

Proposed Mechanism

Targets: ER_Mitochondrial_Axis, Mitochondrial_Function, Autophagy, ER_Stress

Liraglutide (and the dual incretin DA3-CH) were shown to rescue arrested oxidative phosphorylation and glycolysis, mitigate suppressed mitochondrial biogenesis and hyper-polarization of the mitochondrial membrane, and re-establish normalcy of mitochondrial function under chronic ER stress. These effects correlate with a resolution of the Unfolded Protein Response (UPR) and improved autophagosome formation, ultimately reducing synaptic and neuronal death in dopaminergic-like neurons.

Evidence

Level: In vitro (LUHMES dopaminergic-like neurons)

Source: Panagaki et al., 2023. "Incretin Mimetics Restore the ER-Mitochondrial Axis and Switch Cell Fate Towards Survival in LUHMES Dopaminergic-Like Neurons: Implications for Novel Therapeutic Strategies in Parkinson's Disease." J Parkinsons Dis.

Reference: PubMed 37718851

Repurposing Score