Severance Hospital Research Team: "Diabetes Drug Halts Parkinson's Disease Progression"

Blocking the Gut-Brain Axis to Preserve Dopamine Neurons

A study has found that DPP-4 inhibitors, a class of diabetes medications, can halt the progression of Parkinson's disease.

Severance Hospital

The research team led by Professor Jung Seungho of the Department of Neurology at Yongin Severance Hospital, Professor Kim Yeonju of the Department of Biomedical Science at Yonsei University College of Medicine, and Professor Lee Pilhyu of the Department of Neurology at Severance Hospital announced on November 4 that DPP-4 inhibitors block the accumulation of Parkinson's disease-inducing proteins in the gut, thereby suppressing the onset and progression of the disease. The results of this study were published in the international journal Gut (IF 26.2).

Parkinson's disease is the second most common degenerative brain disorder after Alzheimer's disease. It occurs when alpha-synuclein protein accumulates in dopamine neurons in the midbrain, leading to symptoms such as tremors, rigidity, and abnormally slowed movements.

Although the exact cause of alpha-synuclein accumulation in the brain remains unclear, the "gut-brain axis" hypothesis, which suggests that alpha-synuclein aggregates originate in the gut and travel to the brain via the vagus nerve, has been attracting attention.

The research team investigated the possibility of slowing Parkinson's disease progression using sitagliptin, a DPP-4 inhibitor for diabetes treatment. They focused on the fact that, in addition to increasing insulin secretion and lowering blood sugar, DPP-4 inhibitors also have neuroprotective effects.

First, the team induced Parkinson's disease in mice using rotenone, a substance that damages dopamine neurons. When mice were continuously exposed to rotenone, alpha-synuclein aggregates migrated along the gut-brain axis, and after six months, the mice exhibited both loss of dopamine neurons and motor symptoms characteristic of Parkinson's disease.

When sitagliptin was administered concurrently, both inflammatory responses and alpha-synuclein levels in the gut decreased. The loss of dopamine neurons was reduced by nearly half, and improvements in motor function were also observed. Additionally, analysis of gut microbiota revealed an increase in beneficial bacteria and a decrease in harmful bacteria.

To investigate the mechanism of DPP-4 inhibitors, the researchers also restricted the activity of GLP-1 receptors. GLP-1 is a hormone that promotes insulin secretion and lowers blood sugar, and its receptor enables these functions. Even when the GLP-1 receptor was blocked, the inhibitory effect on Parkinson's disease progression remained unchanged. This indicates that DPP-4 inhibitors exert their effects not through the GLP-1 hormone metabolic pathway, but by modulating gut immunity and inflammation.

Professor Jung Seungho stated, "We have confirmed that sitagliptin, a DPP-4 inhibitor, can disrupt the pathological gut-brain axis link in Parkinson's disease," adding, "The fact that sitagliptin's effects persist even when GLP-1 signaling is blocked is strong evidence that this drug acts through immune and inflammatory pathways."

Professor Lee Pilhyu commented, "This study demonstrates that repurposing existing diabetes medications can serve as a strategy to slow the progression of Parkinson's disease," and added, "We have confirmed not only the possibility of slowing disease progression, but also the potential for prevention."

This content was produced with the assistance of AI translation services.