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Reactive astrocytes associated with neuroinflammation are present in tauopathies such as Alzheimer disease (AD), but how these glial cells contribute to the neurodegenerative process remains largely unknown. Now Mann et al. report that levels of astrocytic α2-Na+/K+ adenine triphosphatase (α2-NKA) are elevated in a mouse model of tauopathy and in postmortem brain tissue from patients with AD. Inhibiting α2-NKA with digoxin or α2-NKA shRNAs in a mouse model of tauopathy exerted both preventative and therapeutic effects on tau pathogenesis and brain atrophy, through reductions in astrocyte reactivity, proinflammatory chemokine and cytokine production and levels of the neurotoxic protein LCN2.
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Nature Reviews Drug Discovery21, 260 (2022)
doi: https://doi.org/10.1038/d41573-022-00042-0
References
Mann, C. N. et al. Astrocytic α2-Na+/K+ ATPase inhibition suppresses astrocyte reactivity and reduces neurodegeneration in a tauopathy mouse model. Sci. Transl Med.14, eabm4107 (2022)
