Formation of CSE-YAP complex drives FOXD3-mediated transition of neurotoxic astrocytes in Parkinson’s disease

Astrocytes, constituting the predominant glial cells in the brain, undergo significant morphological and functional transformations amidst the progression of Parkinson's disease (PD). A majority of these reactive astrocytes display a neurotoxic phenotype, intensifying inflammatory responses. Nonetheless, the molecular underpinnings steering neurotoxic astrocyte reactivity during PD progression remain mostly uncharted. Here, we uncover the unique role of cystathionine γ-lyase (CSE) in shaping astrocyte reactivity, primarily channeling astrocytes towards a neurotoxic phenotype, thereby escalating neuroinflammation in PD. Single-cell sequencing data drawn from PD patients coupled with RNA sequencing data from MPP