Diabetes drugs confirm the possibility of suppressing and preventing Parkinson's disease progression

Nov 04, 2025

In animal models administered oral rothenone, the intestinal inflammatory response was confirmed. Alpha-synuclein proteins travel along intestinal epithelial cells and nerves and spread to the midbrain. The coadministration of citagliptin, together with this intestinal inflammatory response, reduced protein accumulation, suppressing alpha-synuclein diffusion into the brain and dopamine neuronal damage.

A study found that a diabetes treatment DPP-4 inhibitor prevents Parkinson's disease from progressing.

A research team led by Professor Jeong Seung-ho of Yongin Severance Hospital, Kim Yeon-joo of Yonsei University's Medical Life Sciences Department, and Professor Lee Pil-Hue of Severance Hospital announced on the 4th that the DPP-4 inhibitor inhibits the onset and progression of Parkinson's disease-causing protein in the intestine.

The results of the study were published in the international academic journal Gut (IF 26.2).

Parkinson's disease is the second most common degenerative brain disease after Alzheimer's. It is caused by the accumulation of alpha-synuclein proteins in midbrain dopamine neurons and shows tremors, stiffness, and abnormally slow behavior.

While the obvious cause of the accumulation of alpha-synuclein proteins in the brain has not been identified, the hypothesis that alpha-synuclein aggregates start in the intestine and travel along the vagus nerve to the brain is drawing attention.

The research team confirmed the possibility of stopping Parkinson's disease progression by using the DPP-4 inhibitor citagliptin, a diabetes treatment. In addition to increasing insulin secretion and lowering blood sugar, DPP-4 inhibitors have a nerve cell protection effect.

First, rothenone, which damages dopamine neurons, caused Parkinson's disease in mice. Continuous exposure of mice to rothenone causes alpha-synuclein aggregates to migrate along the intestinal-brain connecting axis, and after 6 months, Parkinson's disease motor symptoms along with dopamine neuronal cell loss appear.

At this time, the combination of sitagliptin reduced the inflammatory response as well as the alpha-synuclein in the intestine. Dopamine nerve cell loss was reduced by nearly half and motor ability improvement was also confirmed. In addition, when intestinal microorganisms were analyzed, the number of beneficial bacteria increased and the number of harmful bacteria decreased. To examine the principle of action of the DPP-4 inhibitor, we restricted the activity of the GLP-1 receptor. GLP-1 is a hormone that secretes insulin and lowers blood sugar, and receptors help to play this role. Controlling the GLP-1 receptor had the same effect of preventing the progression of Parkinson's disease. This means that DPP-4 inhibitors generate effects through intestinal immunity and inflammation control, not hormonal metabolic pathways through GLP-1.

Professor Jeong Seung-ho confirmed that cytacliptin, a DPP-4 inhibitor, can break the intestinal-brain axis pathological link in Parkinson's disease"The fact that the effect of cytagliptin is maintained even when GLP-1 signaling is blocked is strong evidence that this drug acts through the immune, inflammatory pathway."

Professor Lee Pil-Hugh showed that the drug repurposing strategy of conventional diabetes drugs could lead to inhibitors of Parkinson's disease progression"It even confirmed the possibility that it could be prevented beyond slowing down the progression of Parkinson's disease."," he said.