2026 Undergraduate Research Showcase

Removal of Senescent Cells Attenuates α-Synuclein-Aggregation Mediated Parkinson's Disease Pathology

Document Type

Student Presentation

Presentation Date

4-24-2026

Faculty Sponsor

Dr. Yonghwan Kim and Dr. Dinesh Kumar Verma

Abstract

Emerging evidence suggests that cellular senescence contributes to the progression of neurodegenerative diseases, including Parkinson’s disease (PD). Cellular senescence is a state in which cells cease to proliferate in response to damage and contribute to tissue dysfunction through the release of toxic factors, called Senescence-Associated Secretory Phenotype (SASP). While dopaminergic neurons are the primary cell-type lost in the substantia nigra compacta (SNc) to induce PD, senescent glia (e.g. astrocytes and microglia) are considered to mediate the secondary toxicity in inducing neuronal death. Using the pre-formed fibril (PFF) of alpha-synuclein to induce PD-like pathology, we examined the impact of senolytic treatment to quickly remove senescent glia to prevent the secondary damage in PD pathology. Cellular senescence is assessed by measuring the levels of established cellular markers, as well as morphological changes in immunohistochemistry (IHC) and Western blot analyses. We previously found that PFF injection reduced Lamin B1 and HMGB1 levels and increased p21 expression, particularly in astrocytes and microglia within the striatum and SNc. Our IHC results verified that dopaminergic neuronal loss by PFF in those regions were significantly prevented or reversed by senolytic treatment (ABT-263), which was associated with the reduced number of senescent glia. These findings suggest that removing senescent glia can be a novel therapeutic approach to slow neurodegeneration and progression in PD.

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