MANF
Description
The MANF (mesencephalic astrocyte derived neurotrophic factor) is a protein-coding gene located on chromosome 3.
MANF selectively promotes the survival of dopaminergic neurons in the ventral midbrain. It modulates GABAergic transmission to dopaminergic neurons in the substantia nigra, enhancing spontaneous and evoked GABAergic inhibitory postsynaptic currents. MANF inhibits cell proliferation and cell death induced by endoplasmic reticulum (ER) stress. Under normal conditions, it is retained in the ER/sarcoplasmic reticulum (SR) through association with the ER chaperone protein HSPA5. In response to ER stress and hypoxia, MANF is upregulated and secreted from the ER/SR. After secretion, MANF directly binds to 3-O-sulfogalactosylceramide, a lipid sulfatide found in the outer cell membrane of target cells. This binding promotes MANF uptake by endocytosis, which is essential for its role in alleviating ER stress and cell toxicity under hypoxic and ER stress conditions.
MANF is also known as ARMET, ARP, DDDS.
