Exploring the patterns of Centrin-2: a novel astrocytic marker in health and disease

Centrin-2 (CETN2), a centrosomal protein crucial for DNA repair and maintaining genomic stability, has remained largely unexplored in the context of the human central nervous system (CNS). In this comprehensive study, we examined CETN2 expression in human neuroepithelial stem (NES) cells and pluripotent stem cells. Our findings revealed that CETN2 is predominantly localized to the centrosome in proliferating NES cells. However, as these cells differentiate into mature astrocytes, CETN2's localization undergoes a significant shift, moving from the centrosome to exhibit a widespread cytoplasmic distribution. Further investigation using human brain autopsy samples uncovered a distinct CETN2 expression pattern along the rostro-caudal axis, a distribution not mirrored in murine tissues. In mice, CETN2 expression was largely restricted to ependymal cells. This highlights a species-specific difference in CETN2 localization within the CNS. In glioblastoma multiforme (GBM), CETN2 showed focal accumulation within neoplastic astrocytes, suggesting a potential role in tumor biology. In the context of Alzheimer's disease (AD), CETN2 expression was closely associated with key pathological hallmarks such as neurocognitive decline, amyloid plaques, and neurofibrillary tangles. Notably, CETN2 co-localized with established markers of reactive astrocytes, including STAT3, NFATc3, and YKL-40, suggesting its involvement in the reactive gliosis observed in AD. This study identifies CETN2 as a novel astrocytic marker, expanding its recognized functions beyond centrosomal activity to encompass critical roles in neurodevelopment, glioma biology, and neurodegenerative diseases. These findings provide fresh insights into the complex biology of astrocytes and pave the way for future research into CETN2’s potential as a diagnostic marker or therapeutic target in CNS disorders.