Neurotrophins

Key Biological Properties: Midkine is a basic, low molecular-weight protein composed of two domains held together by disulfide bridges. It is a heparin-binding growth factor with pleiotropic effects, meaning it can influence various biological processes .

Expression Patterns: Midkine is highly expressed during mid-gestation in many organs, including the kidneys, heart, and brain. In adults, its expression is restricted to certain tissues but is upregulated in response to injury, inflammation, and cancer .

Tissue Distribution: In adults, midkine is primarily found in the kidneys, lungs, thyroid, and small intestine. Its expression is also induced in various cancers and during tissue repair processes .

Primary Biological Functions: Midkine promotes cell proliferation, migration, angiogenesis, and fibrinolysis. It plays a significant role in neural development, tissue repair, and cancer progression .

Role in Immune Responses and Pathogen Recognition: Midkine functions as a key player in autoimmune disorders of the central nervous system (CNS) and is involved in neuroinflammation and neurodegeneration. It mediates immune responses by interacting with CNS-resident cells such as astrocytes, microglia, and oligodendrocytes .

Mechanisms with Other Molecules and Cells: Midkine interacts with multiple cell surface receptors to promote growth through effects on cell proliferation, migration, and differentiation. It binds to heparin and other glycosaminoglycans, facilitating its interactions with various receptors .

Binding Partners and Downstream Signaling Cascades: Midkine’s binding partners include proteoglycans, integrins, and receptor tyrosine kinases. These interactions activate downstream signaling pathways such as the Akt, ERK, and HIF1α pathways, which are crucial for cell survival, proliferation, and migration .

Transcriptional Regulation: Midkine expression is regulated by retinoic acid during embryonic development. In adults, its expression is induced by hypoxia, inflammation, and oncogenic signals .

Post-Translational Modifications: Midkine undergoes various post-translational modifications, including disulfide bond formation, which is essential for its biological activity. These modifications influence its stability, localization, and interactions with other molecules .

Biomedical Research: Midkine is a valuable tool in studying neural development, tissue repair, and cancer biology. Its role in neuroprotection and neuroregeneration makes it a promising target for therapeutic interventions in CNS disorders .

Diagnostic Tools: Elevated levels of midkine are associated with various cancers and inflammatory diseases, making it a potential biomarker for diagnosis and prognosis .

Therapeutic Strategies: Midkine-targeted therapies are being explored for treating cancers, autoimmune diseases, and neurodegenerative disorders. Inhibitors and antibodies against midkine are under investigation for their therapeutic potential .

Development: Midkine is crucial during embryonic and fetal development, particularly in the formation of the CNS and other organs. It drives the growth, differentiation, and migration of neural precursor cells .

Aging and Disease: In adults, midkine expression is limited but can be reactivated in response to injury, inflammation, and cancer. Its role in tissue repair and regeneration makes it a key player in aging and disease processes .