Neurotrophins

Pleiotrophin is expressed during embryonic and early postnatal development in the central and peripheral nervous systems, as well as in several non-neural tissues such as the lung, kidney, gut, and bone . In adults, its expression is activity-dependent in the hippocampus and can be induced by ischemic insults or targeted neuronal damage . PTN is also expressed by several tumor cells and is involved in tumor angiogenesis .

Pleiotrophin plays a crucial role in neural development, promoting neurite outgrowth and acting as a mitogen for fibroblasts . It is involved in the proliferation of preadipocytes, pancreatic β cells, and cells during mammary gland development . PTN is essential for the structural integrity of the liver and the neuromuscular junction in skeletal muscle . Additionally, it plays a key role in maintaining glucose and lipid homeostasis and favors oxidative metabolism in skeletal muscle .

Pleiotrophin interacts with various receptors, including receptor protein-tyrosine phosphatase beta/zeta (RPTPβ/ζ), which mediates its effects on cell migration . PTN also binds to cell-surface nucleolin, which can inhibit HIV infection . In the central nervous system, PTN acts as a neuromodulator with multiple neuronal functions, including learning and memory . It is involved in neuroinflammation by modulating microglial activation and cytokine production .

The expression and activity of pleiotrophin are regulated at multiple levels. Transcriptional regulation involves various factors that control PTN gene expression . Post-translational modifications, such as glycosylation and phosphorylation, also play a role in modulating PTN activity . PTN signaling pathways involve interactions with endothelial cells, leading to proliferation, migration, and tube formation .

Pleiotrophin has significant applications in biomedical research, particularly in studying neural development and tumor angiogenesis . It is being explored as a potential therapeutic target for metabolic disorders, given its role in glucose and lipid homeostasis . PTN’s involvement in neuroinflammation and neuroprotection makes it a candidate for therapeutic strategies in neurodegenerative diseases .

Pleiotrophin is highly expressed during embryonic development and early cell differentiation . In adulthood, its expression decreases in most tissues except for the bone and nervous system . PTN levels are associated with advancing age and are involved in tissue regeneration, bone repair, inflammatory processes, hypoxia, tumor growth, and angiogenesis . Its role in maintaining metabolic homeostasis and structural integrity of various tissues underscores its importance throughout the life cycle .