Research

Aging is the primary risk factor for most neurodegenerative diseases, including Alzheimer’s disease (AD) and Parkinson’s disease (PD). Tissues composed primarily of postmitotic cells, such as the brain, are particularly vulnerable to age-related damage. However, the biological mechanisms that connect ageing to neurodegeneration remain poorly understood. Bridging this gap is essential for identifying the early drivers of disease progression and developing novel therapeutic strategies.

Our laboratory investigates the mechanisms of cellular senescence in the brain aging, with the aim of understanding how age-related cellular changes contribute to neurodegenerative diseases. We study how various brain cell types undergo and respond to senescence over time, and how these changes influence neural function and disease vulnerability. Through this research, we seek to uncover mechanistic links between cellular senescence and initiation of disease processes, ultimately contributing to the development of early interventions that preserve brain function.

Glial cells are non-neuronal cells that make up approximately 50% of the brain and play essential roles in supporting and modulating neuronal activity. Astrocytes help maintain the blood–brain barrier, regulate ion homeostasis, and clear excess neurotransmitters from synapses. Microglia serve as the brain resident immune cells mediating neuroinflammation. Oligodendrocytes, which represent the most abundant glial cell type, produce the myelin sheath that insulates neuronal axons and enables efficient signal transmission. Beyond these homeostatic functions, glial cells are increasingly recognized as active contributors to disease processes. Understanding how glia shift from supportive roles to pathological drivers is especially important in the context of neurodegenerative diseases.

Recent studies have identified oligodendrocytes as one of the most significantly altered cell types in neurodegenerative diseases, suggesting their pivotal role in early disease pathogenesis. Building on this, our research investigates how oligodendrocyte dysfunction contributes to neuronal vulnerability and acts as a key regulator in disease progression. Our findings indicate that oligodendrocytes may play a more active role in driving neurodegeneration. By employing a range of glia–neuron cellular platforms and disease-relevant animal modeling, we aim to identify therapeutic targets by mapping glia–neuron crosstalk in the context of neurodegenerative disease.

Neurodegenerative diseases are increasingly recognized as systemic disorders with complex pathophysiology that extends beyond the central nervous system. Among various non-motor symptoms, gastrointestinal (GI) dysfunction is one of the most common and earliest clinical features observed across multiple neurodegenerative conditions. Notably, GI symptoms often precede the onset of classical neurological deficits by several years to decades, highlighting a prolonged prodromal phase and suggesting a possible peripheral origin of disease pathology.

Our laboratory investigates the early pathophysiological mechanisms underlying neurodegenerative diseases, with a particular focus on the gut–brain axis. By generating and applying disease-relevant animal models, we examine cell-type-specific vulnerabilities within enteric neural circuits and study how pathogenic protein species contribute to GI dysfunction and central nervous system degeneration. Through this work, we aim to identify early biomarkers and dissect disease mechanisms, ultimately contributing to the development of preclinical diagnostic tools and peripheral-targeted therapeutic strategies for neurodegenerative disorders.