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DKK2 in ischaemic stroke. After stroke, DKK2 is predominantly released by neurons and is regulated by the transcription factor RXRα. Its levels increase both locally in the brain and systemically in plasma, with additional contributions from leucocytes. During the acute phase of stroke, DKK2 enhances blood-brain barrier (BBB) permeability and promotes neuronal death by inhibiting Wnt signalling. Treatment with anti-DKK2 monoclonal antibodies reduces DKK2 levels and improves BBB integrity and neuronal survival. The remote effects of DKK2, as well as its potential roles in astrocytes, tissue-resident macrophages (tRMs), and during the chronic phases of repair and plasticity, remain to be determined. BBB, blood-brain barrier; DKK2, Dickkopf-related protein 2; LRP5/6, low-density lipoprotein receptor-related protein 5/6; mAB, monoclonal antibody; RXRα, retinoid X receptor alpha; tRM, tissue-resident macrophages; WNT, Wingless-related INTegration site; ?, unknown effect.
Bacigaluppi et al. (Sun,) studied this question.
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