Midkine

Midkine (MDK) is a secreted cytokine and growth factor that signals through cell-surface proteoglycan and non-proteoglycan receptors to regulate inflammatory response, cell proliferation, survival, and tissue regeneration (UniProt: P21741). The protein mediates neutrophil and macrophage recruitment, modulates T cell differentiation, and plays multiple roles in the nervous system by promoting neural precursor survival, neuronal migration, and neurite outgrowth through interactions with heparan sulfate proteoglycans, syndecans, and glypicans. It also binds ALK to activate MAPK and PI3K signaling pathways controlling cell proliferation.

In Alzheimer's Disease, midkine is significantly upregulated in post-mortem AD brain tissue compared to age-matched controls, with a mean log2 fold-change of +1.68 (Chaparral AD proteomics). This upregulation was detected in TMT-labeled quantitative proteomics analysis of subcellular fractions from human brain samples. The elevation of midkine in AD brain may reflect neuroinflammatory processes or compensatory responses to neurodegeneration, given its known roles in inflammation and neuroprotection.