Mesencephalic astrocyte-derived neurotrophic factor (MANF)

Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a highly conserved, secreted protein originally identified for its potent neuroprotective activity, particularly supporting the survival and repair of dopaminergic neurons. Structurally, MANF has an N-terminal saposin-like lipid-binding domain and a C-terminal SAP domain homologous to Ku70, connecting functions in lipid/membrane binding and anti-apoptosis. MANF is both an intracellular and secreted factor, predominantly localized to the endoplasmic reticulum (ER) in many cells, and its expression is strongly induced by ER stress. It modulates the unfolded protein response (UPR) and serves wide-ranging cytoprotective roles in neurons, pancreatic β-cells, and other cell types by supporting survival, proliferation, and adaptation under stress conditions. MANF is a therapeutic candidate for neurodegenerative diseases, diabetes, cardiovascular injury, and certain inflammatory/metabolic disorders, though no approved targeted drugs or therapies exist yet. In diagnostics, urinary MANF is being explored as a non-invasive biomarker for ER stress and kidney injury. Research into MANF’s physiology, mechanisms, and translational potential remains highly active.

Other names

Arginine-rich mutated in early stage of tumors (ARMET)ARPARMET protein

Recombinant MANF exerts **cytoprotective activity**: mitigates ER stress, supports neuron and β-cell survival, reduces apoptosis, and promotes cell repair and proliferation. Modulation of unfolded protein response (UPR) via direct action on intracellular signaling pathways, possibly involving protein kinase C (PKC) activation. Immune modulation (promotes repair phenotype in macrophages). Note: No specific cell-surface receptor for MANF has been identified.