Enzyme Inhibition Shows Promise in Halting Neuron Death in Parkinson’s Disease
Stanford, CA – July 4, 2025 – A new Stanford Medicine-led study offers a potential breakthrough in the fight against Parkinson’s disease, revealing that inhibiting the LRRK2 enzyme can prevent neuron death in mice wiht a specific genetic mutation linked to the disease [[2]]. The findings,published in Science signaling on July 1,suggest a possible treatment strategy for a significant subset of Parkinson’s patients.
The role of LRRK2
The study focuses on Parkinson’s cases caused by a genetic mutation leading to overactivity of the leucine-rich repeat kinase 2 (LRRK2) enzyme. This overactivity disrupts interaction between dopamine-producing neurons and cells in the striatum, a brain region crucial for movement, motivation, and decision-making [[2]]. LRRK2 is a multifunctional protein kinase involved in the development of neurodegenerative diseases, including Parkinson’s [[1]].
How Inhibition Works
Researchers utilized MLi-2, a LRRK2 kinase inhibitor, to decrease the enzyme’s activity. The results showed that inhibiting LRRK2 could stabilize the progression of symptoms, especially when intervention occurs early [[2]].
A key mechanism involves the restoration of primary cilia – cellular appendages that act as “antennae” for receiving chemical signals. Overactive LRRK2 causes cells to lose these cilia, disrupting vital communication pathways. Specifically, the disruption impacts the sonic hedgehog signaling pathway, which is crucial for the production of neuroprotective factors in the striatum [[2]]. Without these factors, cells are more vulnerable to death.
Beyond Genetic Mutations
Importantly, researchers believe the benefits of LRRK2 inhibition may extend beyond cases caused by the specific genetic mutation. As overactive LRRK2 can occur through othre mechanisms, the inhibitor treatment could perhaps help a broader range of parkinson’s patients and even those with other neurodegenerative diseases
