Research Interest

 The BBB protects the brain by restricting the entry of external pathogens (e.g., viruses, bacteria) and toxic substances. Unlike other vascular endothelial cells, BBB endothelial cells have five times more mitochondria and are tightly connected by tight junctions. Our lab has established a mitochondrial dysfunction mouse model in endothelial cells, observing BBB disruption due to reduced tight junctions, infiltration of peripheral immune cells, and neuronal damage. We identified target genes involved in BBB disruption and demonstrated their role in mitigating brain injury in hemorrhagic stroke models. We aim to further explore how the BBB functions as a sensor protecting the brain from peripheral chronic inflammation and how BBB dysfunction contributes to neurodegenerative diseases. 

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra. Exposure to environmental toxins affecting mitochondrial function increases PD risk, but the mechanisms remain unclear. Our lab identified reduced expression of Crif1, a key mitochondrial protein, in the brains of PD patients. We developed a dopaminergic neuron-specific Crif1-deficient mouse model, which mimics the gradual neurodegeneration and motor symptoms seen in PD patients. This model provides new insights into mitochondrial dysfunction in PD pathogenesis and serves as a valuable tool for studying neuroinflammation and vagus nerve involvement in disease progression. 

Astrocytes, which outnumber neurons in the brain, become highly reactive during neuroinflammation. Our research demonstrated that inhibiting dopaminergic neurons using optogenetics induces PD-like symptoms even without neuronal death. Conversely, stimulating these neurons alleviates symptoms. We identified excessive GABA secretion from reactive astrocytes as a key factor in neuronal inhibition. By blocking GABA production using monoamine oxidase B (MAO-B) inhibitors, we restored neuronal function and improved PD symptoms. This study suggests a new therapeutic strategy for PD by targeting astrocyte-mediated inhibitory signaling. Moving forward, we aim to investigate the role of astrocytes in BBB dysfunction under chronic inflammation and their influence on brain-peripheral organ interactions. 

Our lab has focused on mitochondria-driven mechanisms in neurodegenerative diseases, BBB function, and neuroinflammation over the past decade. We are expanding our research to explore the role of the vagus nerve and exosomes in linking peripheral organs with the brain. Beyond local infection and inflammatory responses, we seek to understand how chronic inflammation leads to brain dysfunction and metabolic disorders. Our goal is to develop novel therapeutic approaches that target inter-organ communication pathways, including the BBB, cerebrospinal fluid barrier, vagus nerve, and circulating exosomes, to mitigate chronic inflammation-related neurological diseases.