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Neurodegeneration is accompanied by activation of astrocytes that can have both neuroprotective and neurotoxic functions. Much less is known about how intrinsic dysfunction of astrocytes can lead to neuroinflammation and neurodegeneration. To study astrocyte\u2010driven neurodegeneration, we examined aging cerebella of adult astrocyte\u2010specific Yin Yang1 (\n                    <jats:italic>Yy1<\/jats:italic>\n                    ) conditional knockout mice that contain improperly matured dysfunctional astrocytes. We found that deletion of\n                    <jats:italic>Yy1<\/jats:italic>\n                    from astrocytes during development results in subsequent cerebellar neurodegeneration in adult mice. The neurodegeneration was accompanied by profound changes in astrocyte morphologies and expression of astrocyte\u2010specific genes, and development of severe neuroinflammation that preceded cerebellar neurodegeneration and Purkinje cell (PC) loss. Mechanistically, we found that sustained \u03b2\u2010catenin expression by Bergmann glia (BG) correlated with their decreased adenomatous polyposis coli (APC) expression and diminished expression of synaptic proteins by glutamatergic neurons, suggesting that\n                    <jats:italic>Yy1<\/jats:italic>\n                    supports astrocytic APC expression needed for \u03b2\u2010catenin degradation and proper BG morphology. Our findings highlight the critical role of YY1 in sustaining cerebellar astrocyte functions and suggest that dysfunction of astrocytes has widespread consequences for cerebellar integrity, function, and leads to neurodegeneration.\n                  <\/jats:p>","DOI":"10.1096\/fj.202501225rr","type":"journal-article","created":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T07:00:18Z","timestamp":1752217218000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Defective Astrocyte Maturation Drives Cerebellar Neuroinflammation and Degeneration"],"prefix":"10.1096","volume":"39","author":[{"given":"Karli","family":"Mockenhaupt","sequence":"first","affiliation":[{"name":"Department of Cellular, Molecular, and Genetic Medicine School of Medicine and the Massey Comprehensive Cancer Center, Virginia Commonwealth University  Richmond Virginia 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