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Protein kinase CK2 is a holoenzyme composed of two regulatory (CK2\u03b2) and two catalytic subunits (CK2\u03b1 and CK2\u03b1\u2032) and has been linked to multiple aspects of tau pathology. However, genetic evidence defining the specific contributions of CK2 subunits to tau phosphorylation and tauopathy remains lacking. Elucidating subunit-specific roles is critical for the rational development of CK2-targeted therapies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>To investigate the impact of CK2 in tauopathy, Neuro-2a and primary cell cultures expressing mutant tau were treated with siRNAs targeting the two catalytic subunits of CK2, CK2\u03b1 and CK2\u03b1\u2032. In addition, the PS19 mouse model of tauopathy was bred to be haploinsufficient for the catalytic subunit CK2\u03b1\u2032. Changes in pathology and symptomatology were analyzed via immunohistochemistry, immunoblotting, RNA-sequencing, in situ hybridization, electrophysiology, and Barnes Maze.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We found that the expression of the catalytic subunit CK2\u03b1\u2032, but not catalytic CK2\u03b1 or regulatory CK2\u03b2 subunits, was elevated in postmortem brains of dementia patients and in the hippocampus of PS19 tauopathy mice, especially in neurons and microglia. Using a haploinsufficient model of CK2\u03b1\u2032 in PS19 mice, we demonstrated that the PS19:CK2\u03b1\u2032\n                      <jats:sup>(+\/\u2212)<\/jats:sup>\n                      mice had significantly decreased phosphorylated tau and total tau burden in the hippocampus and cortex. CK2\u03b1\u2032 depletion also attenuated microglial activation, pro-inflammatory cytokine production and microglia synaptic engulfment, and enhanced synaptic gene expression, synaptic density, and long-term potentiation. Importantly, CK2\u03b1\u2032 haploinsufficiency rescued cognitive deficits assessed in the Barnes maze.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Here, we show CK2\u03b1\u2032, one of the two catalytic subunits of CK2, as a novel regulator of tau-mediated neurodegeneration. These effects appear to be mediated through both neuronal and glial functions and may involve CK2\u03b1\u2032-dependent modulation of tau phosphorylation as well as neuroinflammatory and immune signaling pathways. These findings identify CK2\u03b1\u2032 as a mechanistically defined and potentially druggable target for therapeutic strategies aimed at modifying tau-driven neurodegeneration.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s40035-026-00563-3","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T06:51:10Z","timestamp":1783579870000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Protein kinase CK2\u03b1\u2032 as a dual modulator of neuroimmune signaling and synaptic dysfunction in tauopathy"],"prefix":"10.1186","volume":"15","author":[{"given":"Angel","family":"White","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Gavrilyuk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Persephone","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Falcon-Moya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reid","family":"Thurston","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amal","family":"Fickak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas B.","family":"Rozema","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prarthana","family":"Keshavaram","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Vermilyea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riley","family":"Schlichte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joyce","family":"Meints","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfonso","family":"Araque","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael K.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rocio","family":"Gomez-Pastor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,9]]},"reference":[{"issue":"1-3","key":"563_CR1","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1159\/000283478","volume":"7","author":"B Kovacech","year":"2010","unstructured":"Kovacech B, Skrabana R, Novak M. 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